NPM--ALK

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NPM ALK

COSMIC

The fusion gene pair NPM--ALK information is not available in COSMIC database.

ChimerKB

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The fusion gene pair NPM--ALK information is not available in CHIMERKB (CHIMERDB 3.0) database.

ChimerPUB

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The fusion gene pair NPM--ALK information is available in CHIMERPUB (CHIMERDB 3.0) database.

Fusion_pairTranslocationPMIDDiseaseValidationGene TypeSentence_highlight
NPM_ALKinv(2)(p23q35) / t(2;5)(p23;q35) / t(1;2)(q25;p23) / t(2;5) / 10702393non Hodgkin Lymphoma FISH - The subset of CD30-positive anaplastic large cell lymphomas (ALCL) with the NPM-ALK gene fusion arising from the t(2;5)(p23;q35) forms a distinct clinical and prognostic entity. /// "In a screen for variant ALK gene fusions, we identified two ALCL that were negative for NPM-ALK by reverse transcriptase-polymerase chain reaction, but were positive for cytoplasmic ALK with both polyclonal and monoclonal antibodies to the ALK tyrosine kinase domain, consistent with ALK deregulation by an alteration other than the t(2;5) Case 1 was a T-lineage nodal and cutaneous ALCL in a 52-year-old woman, and Case 2 was a T-lineage nodal ALCL in a 12-year-old girl. "
NPM_ALKt(2;5)(p23;q35) / inv(2)(p23q35) / 9250148anaplastic large cell lymphoma;lymphoma FISH - Two additional ALK1-positive cases with an abnormal karyotype, but without t(2;5)(p23;q35), showed by fluorescence in situ hybridization analysis a cryptic NPM/ALK gene fusion caused by an insertion of ALK near NPM in one case and a translocation of ALK to 2q35 as a result of an indiscernible inv(2)(p23q35) in the other.
NPM_ALKt(2;5) / t(2;5) / 10552961anaplastic large cell lymphoma;lymphoma FISH;PCR;RT-PCR - The absence of the NPM-ALK fusion gene was confirmed by reverse transcriptase-polymerase chain reaction (RT-PCR) in 8 cases and by fluorescence in situ hybridization (FISH) analysis in a further 2 cases. /// "These results suggest that lymphomas carrying variants of the NPM-ALK fusion protein can be detected by immunostaining for ALK and NPM and also that they can be grouped with classical t(2;5)-positive tumors as a single entity (ALK-positive lymphoma or ""ALKoma"") that shows a better prognosis than ALK-negative anaplastic large-cell lymphoma.. " /// " The tumor cells in ALK-positive lymphoma (""ALKoma"") usually express the product of the NPM-ALK chimeric gene, generated by the t(2;5) chromosomal translocation. " /// "In each case, ALK staining was restricted to the cytoplasm and the N-terminus of NPM to the nucleus (contrasting with lymphomas expressing NPM-ALK in which cytoplasmic as well as nuclear labeling is seen). " /// "However, 10% to 20% of ALK-positive lymphomas express ALK fusion protein(s) other than NPM-ALK, and in this report, we describe the immunohistologic and clinicopathologic features of 15 such cases. " /// Lymphomas expressing ALK fusion protein(s) other than NPM-ALK..
NPM_ALKt(2;5)(p23;q35) / t(2;5) / t(2;5) / 9057650Hodgkin disease;non Hodgkin Lymphoma FISH - This NPM-ALK FISH assay was initially validated by analysis of a series of cytogenetically characterized cell lines, with the presence of the der(5) chromosome showed specifically only in those lines known to contain the t(2;5). /// Detection of the t(2;5)(p23;q35) and NPM-ALK fusion in non-Hodgkin's lymphoma by two-color fluorescence in situ hybridization..
NPM_ALKinv(2)(p23q35) / t(2;5)(p23;q35) / t(2;5) / 9763551non Hodgkin lymphoma;anaplastic large cell lymphoma;lymphoma FISH - Moreover, a striking association of the inv(2)(p23q35) with a secondary chromosomal change, viz, ider(2)(q10)inv(2)(p23q35), carrying two additional copies of the putative ALK-related fusion gene, was found in all three patients, suggesting that, in contrast to the standard t(2;5)/NPM-ALK fusion, multiple copies of the putative 2q35-ALK chimeric gene may be required for efficient tumor development. /// "In contrast to ALCL cases with the classical t(2;5)(p23;q35) that usually show both cytoplasmic and nuclear or predominantly nuclear alone localization of the NPM-ALK chimeric product, in all three cases with an inv(2)(p23q35) the ALK protein accumulated in the cytoplasm only, supporting the previous assumption that the oncogenic potential of ALK may not be dependent on its nuclear localization. "
NPM_ALKt(2;5)(p23;q35) / inv(2)(p23q35) / t(2;17)(p23;q25) / 11395396anaplastic large cell lymphoma;lymphoma FISH;PCR;RT-PCR - The aims of the present study were to investigate the presence of NPM-ALK and ATIC-ALK fusion genes in ALCL, using a real-time 5' exonuclease-based reverse-transcription polymerase chain reaction (RT-PCR). /// The NPM-ALK and the ATIC-ALK fusion genes can be detected in non-neoplastic cells.. /// "Our findings demonstrate that NPM-ALK and ATIC-ALK fusion transcripts may be detected in conditions other than ALK-positive ALCL including reactive lymphoid tissues, although at low levels, suggesting the presence of the transcripts in normal (bystander) cells. " /// RT-PCR detected the NPM-ALK and ATIC-ALK fusions at high levels in 8 and 3 of a total of 13 ALK-positive ALCL cases. /// "Similarly, out of the three strongly positive ATIC-ALK cases, one case was positive for the NPM-ALK fusion, at low levels. " /// "In addition, of the eight ALK-positive ALCL cases that were strongly positive for the NPM-ALK fusion, three cases also showed the presence of the ATIC-ALK fusion, although at much lower levels. " /// "Finally, the NPM-ALK and the ATIC-ALK fusions were detected, at equally low levels, respectively in 13 and 5 ALK-negative ALCL cases, in 11 and 5 Hodgkin's disease cases and in 20 and 1 non-neoplastic lymphoid tissues. "
NPM_ALK- 12505251non Hodgkin Lymphoma FISH - The NPM/ALK fusion gene was confirmed by fluorescence in situ hybridization (FISH) analysis in more than 80% of interphase nuclei and metaphase spreads. /// The chromosomal 5q35 breakpoint (bp) and the expression of the NPM/ALK fusion gene are the most remarkable molecular cytogenetic features of these malignancies. /// "To identify new locations of ALCL-related oncogenes, comparative genomic hybridization (CGH) was applied to three ALCL cell lines (SU-DHL-1, Karpas 299, and DEL) exhibiting the 5q35 bp and expressing the NPM/ALK transcript. "
NPM_ALKt(2;5)(p23;q35) / 22726922anaplastic large cell lymphoma;lymphoma FISH - ALK-positive ALCL is characterized by t(2;5)(p23;q35)/NPM-ALK or variant ALK-involved translocations, while little is known about the genetic changes in ALK-negative ALCL.
NPM_ALKt(2;5) / 9138611non Hodgkin lymphoma;lymphoma FISH;PCR - Molecular equivalents of chromosomal translocations generate either a qualitative change due to the expression of a chimaeric, relatively tumour specific, protein, such as the NPM-ALK associated with the t(2;5) in ALCL or a quantitative change in the extent, stage or site of expression of a full length protein, due to its juxtapositioning to and deregulation by an Ig or TCR gene. /// "At diagnosis, immunological detection of the deregulated 'protooncogene' may well provide the simplest, most appropriate screening technique for CCND1 and NPM-ALK induced ALK expression. "
NPM_ALKt(2;5)(p23;q35) / 16954669anaplastic large cell lymphoma;non Hodgkin lymphoma;lymphoma FISH - In the majority of cases, ALCL are of T-cell origin and contain the t(2;5)(p23;q35) leading to an NPM-ALK fusion or variant ALK translocations.
NPM_ALKt(2;5) / t(2;5) (p23;q35) / 9684923non Hodgkin Lymphoma FISH;PCR;RT-PCR - these results must be confirmed in prospective studies of patients with uniform staging and therapy to more fully understand the clinical significance of the t(2;5) and its novel chimeric protein, NPM-ALK.. /// "Multiple techniques including reverse transcriptase-polymerase chain reaction (RT-PCR) amplification of NPM-ALK fusion transcripts, genomic DNA-PCR, RNA in situ hybridization, and fluorescence in situ hybridization (FISH) of metaphase chromosomes and interphase nuclei, and immunohistochemical detection of the 80 kilodalton protein (p80) derived from the NPM-ALK fusion have enabled surveys of normal and lymphoma tissues for evidence of the translocation. " /// "In lymphoma, NPM-ALK expression is most often seen in young patients with the monomorphic or small-cell variant of ALCL who present with advanced stage disease and have tumors with a CD30+, T- or null-cell phenotype. " /// "NPM-ALK is rarely, if ever, detected in Hodgkin's disease or secondary ALCL. " /// A retrospective study has suggested that expression of NPM-ALK is associated with a better overall 5-year survival. /// "In addition, expression of NPM-ALK has been found in occasional CD30 negative B-cell lymphomas with diffuse large cell or immunoblastic histology. " /// "Although initially found in primary nodal ALCL, recent studies suggest that NPM-ALK expression may occur in lymphoma at extranodal sites, including the skin. " /// "it remains controversial, however, whether CD30+ primary cutaneous lymphoma and its benign counterpart, lymphomatoid papulosis (LyP), express NPM-ALK in some cases. " /// "This translocation creates a novel fusion protein, NPM-ALK, which has transforming properties in vitro and can cause large-cell lymphoma in vivo when transfected into murine bone marrow. "
NPM_ALK- 23588372B cell lymphoma;lymphoma FISH - The gene fusion product and the transcription factor STAT3 are both phosphorylated, and thereby the pathogenetic mechanism of this case shows important analogies with that of NPM-ALK and CLTC-ALK lymphomas, in which STAT3 plays a central role in the lymphomagenesis.
NPM_ALKt(2;5) / t(2;5)(p23;q35) / 10555007anaplastic large cell lymphoma;lymphoma FISH;PCR;RT-PCR - RT-PCR, performed on 21 lymphomas, detected NPM-ALK mRNA in five of the lymphomas, all of which reacted with anti-ALK1 and showed ALK gene rearrangement by FISH.
NPM_ALKdel(11)(q21q23) / p22;q23q23 / 15188459hematologic malignancy FISH;PCR;RT-PCR - Alternate and cytogenetically undetectable mechanisms of fusion transcript generation have been documented for BCR-AB1, AML1-ETO, PML-RARA, NPM/ALK, and MLL-MLLT2 (AF4).
NPM_ALK- 14631806anaplastic large cell lymphoma;anaplastic large cell lymphoma;lymphoma FISH;PCR - The morphological investigations are supplemented by karyotyping and/or by a demonstration of breakpoint at 2p23 harboring ALK gene (FISH), and by molecular detection of chimeric genes characteristic of ALK+ lymphomas (NPM-ALK, ATIC-ALK, TPM3-ALK, TFG-ALK, and some even rarer rearrangements).
NPM_ALKt(2;5) / 15921012anaplastic large cell lymphoma;B cell lymphoma;lymphoma FISH - Genetic studies showed that the majority of ALK+DLBCL cases are characterized by the clathrin (CLTC)-ALK fusion and in a few cases the NPM-ALK rearrangement has been found..
NPM_ALK- 18275429anaplastic large cell lymphoma;lymphoma FISH - ALK-positive ALCL with NPM-ALK or other ALK variant translocations showed a similar profile of secondary genetic alterations.
NPM_ALKt(2;5)(p23;q35) / 11943732anaplastic large cell lymphoma;lymphoma - - In most of these tumors, the t(2;5)(p23;q35) generates the NPM-ALK fusion gene. /// Transfection experiments using NIH-3T3 fibroblasts showed a similar transforming efficiency of TFG-ALK variants compared with NPM-ALK. /// "In addition, in common with NPM-ALK, the TFG-ALK proteins formed stable complexes with the signaling proteins Grb2, Shc, and PLC-gamma. " /// "In conclusion, these findings indicate that the TFG may use a variety of intronic breakpoints in ALK rearrangements generating fusion proteins of different molecular weights, but with similar transforming potential than NPM-ALK.. "
NPM_ALKt(2;5) (p23;q35) / 8683377anaplastic large cell lymphoma;lymphoma PCR;RT-PCR - The fusion gene NPM-ALK occurs in a subset of anaplastic large cell lymphomas (ALCLs), as a result of a chromosomal translocation, t(2;5) (p23;q35). /// Molecular analysis of the NPM-ALK rearrangement in Hodgkin's disease.. /// The expected 177 bp product indicative of the NPM-ALK rearrangement was identified in Karpas 299 and SUDHL-1 cell lines and in two out of eight ALCLs. /// "In order to check this hypothesis, reverse transcriptase-polymerase chain reaction (RT-PCR) was performed to detect the hybrid NPM-ALK gene in 30 tumour samples, including 22 lymph node biopsies from HD and eight ALCL specimens. "
NPM_ALKt(2;5) / 9561912malignant histiocytosis - - These in vitro studies have demonstrated that the proliferation is characterized by a unique chromosomal abnormality, the 5q35bp usually associated with a t(2;5) translocation generating a fusion gene NPM/ALK and the subsequent translation of p80 protein. /// "In view of these chromosomal aberrations, the CD30+ ALCLs represent a heterogeneous group because 15% to 50% express the NPM/ALK fusion gene. "
NPM_ALKt(2;5)(p23;q35) / t(2;3)(p23;q21) / t(2;5) / 10556217anaplastic large cell lymphoma;lymphoma - - Anaplastic large cell lymphoma (ALCL) is associated with the t(2;5)(p23;q35), which generates the NPM-ALK fusion gene encoding an 80-kD protein.
NPM_ALKt(2;5) / 21380699non Hodgkin Lymphoma - - Until recently, recurrent genetic abnormalities characteristic of the large-cell lymphomas had not been identified.However, the characterization during the past 2 yr of chromosomal rearrangements mvolvmg the BCL6/LAZ3 zmc finger gene located at 3q27 (which is altered m approx 30% of these tumors [2,3]), and the cloning by our group (4) of the NPM-ALK fusion gene produced by the t(2;5) may now permrt the identrficatton of molecular genetic subtypes of largecell lymphoma that possess unique btological and/or clinical features.. /// NPM-ALK Reverse Transcriptase-Polymerase Chain Reaction Analysis for Detection of the t(2;5) Translocation of Non-Hodgkin's Lymphoma..
NPM_ALKt(5;17) / t(5;17)(q32;q12) / t(2;5) / t(15;17) / t(11;17) / 8562957acute promyelocytic leukemia;leukemia;lymphoma - - The NPM sequences contained in the shorter NPM-RAR cDNA are identical to the NPM sequences contained in the NPM-ALK fusion gene expressed in t(2;5) lymphomas.
NPM_ALKt(2;5) (p23;q35) / 15588951anaplastic large cell lymphoma - - Anaplastic large-cell lymphomas (ALCL) are frequently associated with the chromosomal translocation t(2;5) (p23;q35) resulting in the NPM/ALK fusion gene that encodes a constitutively activated tyrosine kinase. /// NPM/ALK downregulates p27Kip1 in a PI-3K-dependent manner.. /// In this study we investigated the role of PI-3K/AKT in NPM/ALK-dependent downregulation of p27Kip1 protein. /// "p27Kip1 was found to be downregulated in NPM/ALK-transformed hematopoietic cells, but inhibition of proteasome-dependent degradation pathway by epoxomicin reversed this effect. " /// "Taken together, we postulate that NPM/ALK-PI-3K pathway stimulates cell proliferation by regulation of the expression and nuclear localization of p27Kip1.. " /// "To investigate this phenomenon the pro-B cell line BaF3, BaF3 cell line stably expressing NPM/ALK, and ALCL SUP-M2 cell line were used. " /// We showed that NPM/ALK stimulated cell proliferation and that PI-3K/AKT pathway played an important role in this effect.
NPM_ALKt(14;18) / t(11;14) / 22450142leukemia - - The authors review the literature concerning monoclonal B-cell lymphocytosis, and the occurrence of chromosomal translocations t(14;18) and t(11;14), NPM-ALK fusion gene, JAK2 V617F mutation, BCR-ABL1 fusion gene, ETV6-RUNX1(TEL-AML1), MLL-AF4 and PML-RARA fusion gene in healthy individuals.
NPM_ALKt(2;5)(p23;q35) / t(2;5) / 25961700anaplastic large cell lymphoma;lymphoma - - In 1994, the t(2;5) was cloned and the NPM-ALK fusion gene generated by this rearrangement was identified.
NPM_ALKt(2;5)(p23;q35) / 17116485acute lymphoblastic leukemia;anaplastic large cell lymphoma;lymphoblastic leukemia;non Hodgkin lymphoma - - Chromosomal abnormalities, including t(2;5)(p23;q35), the ALK/NPM fusion gene, and complex karyotypes with multiple additional abnormalities, were identified in all three patients. /// Pediatric ALCL cases frequently have complex karyotypes and usually involve ALK/NPM translocations in this limited study.
NPM_ALKt(2;5)(p23;q35) / t(2;5) / 11532349anaplastic large cell lymphoma;lymphoma - - The t(2;5)(p23;q35) translocation creates a fusion gene NPM-ALK (p80) that encodes a product with tyrosine kinase activity believed to play an important role in development of anaplastic large cell lymphoma (ALCL). /// "Following herbimycin A treatment, a decrease in tyrosine kinase activity in the ALCL cell lines and inhibition in NPM-ALK (p80) autophosphorylation was demonstrated by immunoprecipitation and Western blotting. " /// Inhibition of tyrosine kinase activity induces caspase-dependent apoptosis in anaplastic large cell lymphoma with NPM-ALK (p80) fusion protein..
NPM_ALKp23;q35 / t(2;5) / 10994999anaplastic large cell lymphoma;non Hodgkin lymphoma;B cell lymphoma;lymphoma PCR;RT-PCR - Cloning the translocation breakpoint and identifying the ALK and NPM genes provided tools for screening material from patients with ALCL using various approaches at the chromosome, DNA, RNA, or protein level: positive signals in the reverse transcriptase-polymerase chain reaction (RT-PCR) and the immunostaining with anti-ALK monoclonal antibodies (McAb) serve as the most convenient tests for detection of the t(2;5) NPM-ALK since the fusion gene and ALK protein expression do not occur in normal or reactive lymphoid tissue. /// Pathobiology of NPM-ALK and variant fusion genes in anaplastic large cell lymphoma and other lymphomas.. /// "Positivity for NPM-ALK is associated to various degrees with the following parameters: 44% and 45% of ALCL cases with T cell and Null cell immunophenotype, respectively, are positive, whereas only 8% of cases with a B cell immunoprofile are positive. " /// The wide range of NPM-ALK positivity reported in different series appears to be dependent on the inclusion and selection criteria of the ALCL cases studied. /// The NPM-ALK chimeric gene encodes a constitutively activated tyrosine kinase that has been shown to be a potent oncogene.
NPM_ALKt(2;5) / t(2;5) / 21312108non Hodgkin lymphoma;lymphoma - - Recently, however, two recurrent genetic abnormalities in large-cell NHL-activation of the BCL6/LAZ3 zinc finger gene located at 3q27 (altered in approx 30% of large-cell lymphomas [2-4]) and the NPM-ALK fusion gene (5-7) produced by the t(2;5)-have been analyzed to now permit the identification of patient subsets that have reproducibly different therapeutic responses and survival rates in most studies, both of these molecular genetic subtypes appearing to have a superior prognosis compared to those cases lacking these gene abnormalities.. /// NPM-ALK Reverse Transcriptase-Polymerase Chain Reaction for Detecting the t(2;5) of Non-Hodgkin's Lymphoma..
NPM_ALKt(2;5) / 9547986anaplastic large cell lymphoma;sarcoma;lymphoma - - The NPM/ALK gene fusion in the pathogenesis of anaplastic large cell lymphoma.. /// The cloning of the t(2;5) translocation breakpoints and the identification of the NPM/ALK fusion in Ki-1 ALCL have brought forth from this heterogeneous morphological grouping a subset of cases defined by an aetiological genetic alteration. /// Systems developed to inhibit other fusion transcripts and oncogenic tyrosine kinases can now be applied to NPM/ALK positive lymphomas. /// "Such novel approaches could target NPM/ALK at the level of the genomic sequence, transcript, protein or its downstream targets, when the latter are further elucidated. " /// It has also confirmed that HD is pathogenetically unrelated to NPM/ALK positive Ki-1 ALCL. /// The analysis of NPM/ALK positive lymphomas as a single clinicopathological entity has already begun to clarify and explain some previous clinical observations in Ki-1 ALCL. /// "Although much work remains to be done on the mechanism of NPM/ALK lymphomagenesis, rational treatment approaches are now within reach. "
NPM_ALK- 8616079malignant histiocytosis PCR;RT-PCR - NPM/ALK gene fusion transcripts identify a distinct subgroup of null type Ki-1 positive anaplastic large cell lymphomas.. /// "The specific translocation was found exclusively in six childhood tumours previously diagnosed as malignant histiocytosis (MH), whereas all adult lymphomas (three ALCL without characteristics of MH, three secondary ALCL following HD) and two paediatric cases of secondary ALCL following HD did not show NPM/ALK gene fusion products. " /// Our data indicate a high association of previously diagnosed MH and NPM/ALK gene rearrangements. /// "We performed NPM/ALK RT-PCR on 14 cases of ALCL expressing distinct myelomonocytic markers, e.g. "
NPM_ALK- 9269795hodgkin disease - - NPM-ALK gene fusion and Hodgkin's disease..
NPM_ALKt(2;5) / t(14;18) / t(9;22) / t(2;5) / 9886332non Hodgkin Lymphoma PCR;RT-PCR - We conclude that NPM/ALK fusion genes are present in peripheral blood cells of healthy donors. /// "To further delineate the relevance of this finding for HD, we studied the occurrence of NPM/ALK fusion genes in peripheral blood cells of healthy donors by RT-PCR. " /// Detection of the t(2;5)-associated NPM/ALK fusion cDNA in peripheral blood cells of healthy individuals.. /// "Due to the low rate of NPM/ALK-positive cells in the peripheral blood of positive individuals, an assignment to a defined cellular subpopulation was not possible. " /// Our group recently demonstrated NPM/ALK fusion cDNAs by single-cell RT-PCR in < 3% of CD30+ tumour cells in 2/9 cases of HD. /// NPM/ALK fusion cDNAs were found by RT-PCR in 14/29 healthy individuals and confirmed by hybridization with a breakpoint-specific oligonucleotide.
NPM_ALKt(2;5)(p23;q35) / 7772531anaplastic large cell lymphoma PCR - We have developed a PCT methodology which has enabled the detection of the NPM-ALK rearrangements amongst seven t(2;5)(p23;q35) ALCL cases based on a long-range PCR of genomic DNA. /// Detection of NPM-ALK DNA rearrangement in CD30 positive anaplastic large cell lymphoma..
NPM_ALKt(2;5)(p23;q35) / t(2;5) / t(2;5) / 14736822- PCR;RT-PCR - DNA sequencing of the RT-PCR products from total and aRNA of SU-DHL-1 cells demonstrated identical sequences corresponding to the NPM-ALK fusion gene. /// "RT-PCR using cDNA from the resultant amplified (a) RNA and total RNA resulted in the 177 bp NPM-ALK fusion gene product from the SU-DHL-1 cell line, but not from aRNA or total RNA from the HUT-78 cell line. " /// Utility of linearly amplified RNA for RT-PCR detection of chromosomal translocations: validation using the t(2;5)(p23;q35) NPM-ALK chromosomal translocation..
NPM_ALKt(9;22) / t(14;18) / t(2;5) / t(9;22) / t(14;18) / 11907785acute lymphoblastic leukemia;anaplastic large cell lymphoma;lymphoblastic leukemia;leukemia;follicular lymphoma PCR - In peripheral blood of at least 50% of healthy individuals, the translocations t(9;22) BCR/ABL, t(14;18) IgH/BCL-2, t(2;5) NPM-ALK and MLL duplications, which characterize chronic myelogenous leukemia and acute lymphoblastic leukemia, follicular lymphoma, anaplastic large cell lymphoma, and acute myelogenous leukemia, respectively, are detectable by sensitive polymerase chain reaction (PCR).
NPM_ALKt(2;5)(p23;q35) / 23619105anaplastic large cell lymphoma;B cell lymphoma;lymphoma - - NPM-ALK/t(2;5)(p23;q35) is a genetic hallmark of ALK anaplastic large cell lymphoma (ALCL).
NPM_ALKt(2;5)(p23;q35) / t(2;5) / 9121481non Hodgkin lymphoma;lymphoma - - Cell fractionation studies of the t(2;5) translocation-containing lymphoma cell line SUP-M2 showed NPM-ALK to be localized within both the cytoplasmic and nuclear compartments. /// "This engineered TPR-ALK hybrid protein, which transformed cells almost as efficiently as NPM-ALK, was localized solely within the cytoplasm of cells. " /// "Further, the activation of the truncated ALK protein by a completely heterologous oligomerization domain suggests that the functionally important role of the NPM segment of NPM-ALK in transformation is restricted to the formation of kinase-active oligomers and does not involve the alteration of normal NPM functions.. " /// Sedimentation gradient experiments revealed that NPM-ALK forms in vivo multimeric complexes of approximately 200 kDa or greater that also contain normal NPM. /// "These data indicate that the nuclear and nucleolar localization of NPM-ALK, which probably occur because of transport via the shuttling activity of NPM, is not required for oncogenesis. " /// Immunostaining performed with both polyclonal and monoclonal anti-ALK antibodies confirmed the dual location of the oncoprotein and also indicated that NPM-ALK is abundant within both the nucleoplasm and the nucleolus. /// "Here, we demonstrate the transforming ability of NPM-ALK and show that oncogenesis by the chimeric protein requires the activation of its kinase function as a result of oligomerization mediated by the NPM segment. "
NPM_ALKt(2;5) / 17073594- - - In human non-Hodgkin lymphomas, the NPM-ALK oncogene arising from the t(2;5) chromosomal translocation represents the most important oncogenic tyrosine kinase identified so far. /// Targeting the oncogenic tyrosine kinase NPM-ALK in lymphoma: the role of murine models in defining pathogenesis and treatment options.. /// "Here, the latest developments in the analysis of NPM-ALK induced lymphomagenesis by murine models is reviewed.. "
NPM_ALKt(2;5) / 11266530anaplastic large cell lymphoma;lymphoma - - Subsequently, a characteristic cytogenetic abnormality was identified, the t(2;5), that led to identification of the genes involved in the translocation (NPM/ALK) and insights into the pathogenesis.
NPM_ALKt(2;5)(p23;q35) / t(1;2)(q25;p23) / t(2;3)(p23;q21) / t(2;17)(p23;q23) / inv(2)(p23q35) / 15208656anaplastic large cell lymphoma;lymphoma - - Majority of anaplastic large-cell lymphomas (ALCLs) are associated with the t(2;5)(p23;q35) translocation, fusing the NPM (nucleophosmin) and ALK (anaplastic lymphoma kinase) genes (NPM-ALK). /// "Although overexpression of NPM-ALK has previously been shown to transform fibroblasts, the transforming potential of variant X-ALK proteins has not been precisely investigated. " /// "We stably transfected the cDNAs coding for NPM-ALK, TPM3-ALK, TFG-ALK, CLTC-ALK or ATIC-ALK into nonmalignant NIH3T3 cells. "
NPM_ALKt(2;5) / 22192458anaplastic large cell lymphoma;neuroblastoma;lymphoma - - The catalytic domain of ALK was originally identified in the t(2;5) translocation that produces the unglycosylated oncogenic protein NPM-ALK, which occurs in Anaplastic Large Cell Lymphoma (ALCL). /// "On the contrary, tunicamycin had no effects on NPM-ALK phosphorylation in SU-DHL1 cells. " /// "As a control, we used the NB cell lines LA1-5S and NB5 (no ALK expression), and the ALCL cell line SU-DHL1 (NPM-ALK). "
NPM_ALKp23;q35 / t(2;5) / t(2;5) / 8558920Hodgkin disease PCR;RT-PCR - In a first step, the expression of the NPM-ALK fusion gene was examined by reverse transcriptase-polymerase chain reaction (RT-PCR). /// The NPM-ALK fusion transcript and the p80 protein were detected in eight of nine ALCL cell lines.
NPM_ALKt(2;5)(p23;q35) / 12644020anaplastic large cell lymphoma;lymphoma - - Approximately 60% of all anaplastic large-cell lymphomas (ALCL) contain a specific t(2;5)(p23;q35) chromosomal translocation leading to overexpression of NPM-ALK. /// Hammerhead ribozyme-mediated cleavage of the fusion transcript NPM-ALK associated with anaplastic large-cell lymphoma.. /// "Constant transfection of Karpas 299 cells with RZ1* for 96 hours did not lead to a significant reduction of NPM-ALK protein, presumably due to the long half-life of NPM-ALK (48 hours). " /// We designed five anti-ALK hammerhead ribozymes that were targeted to cleave the ALK proportion of NPM-ALK. /// Ribozyme performance was tested in 293 cells (cotransfected with NPM-ALK) and in the ALCL cell line Karpas 299 by transient and stable transfection and Western blotting. /// Stable transfection of Karpas 299 cells with pRZ1 also resulted in significant reduction of NPM-ALK expression. /// The half-life time of NPM-ALK was determined by pulse-chase experiments. /// These results suggest that ribozymes targeted against NPM-ALK are able to inhibit expression of this oncogenic kinase efficiently and will be a useful tool to analyze its role in the pathophysiology of ALCL.. /// "In contrast, NPM-ALK protein expression was almost completely suppressed in transiently transfected 293 cells. " /// "As the chimeric tyrosine kinase is involved in tumorigenesis and pathogenesis of ALCL, we were interested to inhibit NPM-ALK expression using an exogenous and an endogenous ribozyme approach. "
NPM_ALKt(2;5)(p23;q35) / t(2;5) / t(2;5) / 11178628anaplastic large cell lymphoma;lymphoma PCR;RT-PCR - ALK abnormalities were evaluated by assay for the t(2;5)(p23;q35) translocation by RT-PCR and/or expression of NPM-ALK fusion protein by immunohistochemistry.
NPM_ALKt(2;5) / 17690253anaplastic large cell lymphoma;anaplastic large cell lymphoma;lymphoma - - ALK fusions occur in approximately 50% of ALCLs, and among these, 80% have the t(2;5) translocation with NPM-ALK expression. /// The oncoprotein NPM-ALK of anaplastic large-cell lymphoma induces JUNB transcription via ERK1/2 and JunB translation via mTOR signaling.. /// Expression of NPM-ALK results in ERK1/2 activation and transcriptional up-regulation of JUNB. /// "In conjunction with NPM-ALK, JunB enhances cell cycle progression and may therefore represent a therapeutic target.. "
NPM_ALKt(2;5) / 19887607anaplastic large cell lymphoma;T cell lymphoma;lymphoma - - The majority of ALCL carries the translocation t(2;5) that encodes for the oncogenic tyrosine kinase NPM-ALK, fundamental for survival, proliferation, and migration of transformed T cells. /// "We further show that NPM-ALK, but not the kinase-dead NPM-ALK(K210R), downregulated the expression of these molecules by a STAT3-mediated gene transcription regulation and/or epigenetic silencing because this downregulation was reverted by treating ALCL cells with 5-aza-2-deoxycytidine or by knocking down STAT3 through short hairpin RNA. " /// NPM-ALK oncogenic tyrosine kinase controls T-cell identity by transcriptional regulation and epigenetic silencing in lymphoma cells.. /// "Finally, NPM-ALK increased the methylation of ZAP70 intron 1-exon 2 boundary region, and both NPM-ALK and STAT3 regulated the expression levels of DNA methyltransferase 1 in transformed T cells. "
NPM_ALK- 17320171anaplastic large cell lymphoma;lymphoma PCR;RT-PCR - Quantitative PCR detection of NPM/ALK fusion gene and CD30 gene expression in patients with anaplastic large cell lymphoma--residual disease monitoring and a correlation with the disease status.. /// ALCL is frequently associated with a NPM/ALK fusion gene which is found in up to 75% of pediatric ALCLs. /// RQ-RT-PCR of NPM/ALK expression is a promising and rapid approach for monitoring MRD.. /// Five out of nine relapses were preceded or were accompanied by minimally half log increased NPM/ALK levels in the BM. /// "In all BM samples from relapses and/or closely before a relapse, BM samples revealed NPM/ALK and CD30 positivity in at least one of the iliac BM trephines. " /// Real-time quantitative RT-PCR (RQ-RT-PCR) of NPM/ALK and CD30 gene expression was employed to analyze minimal residual disease (MRD) in 10 patients with NPM/ALK positive ALCL in 79 follow-up bone marrow (BM) and/or peripheral blood (PB) samples.
NPM_ALK- 23978023anaplastic large cell lymphoma;lymphoma PCR;RT-PCR - [Prognostic significance of the NPM-ALK fusion gene in bone marrow and peripheral blood for patients with anaplastic large cell lymphoma].. /// To investigate the expression of NPM- ALK fusion gene in bone marrow (BM) and peripheral blood (PB) in anaplastic large cell lymphoma (ALCL) patients and its prognostic significance. /// "NPM- ALK fusion gene of 21 BM and 15 PB samples from patients with NPM-ALK positive ALCL was detected by RT- PCR, and the relationship between NPM- ALK expression and prognosis and clinical characters was evaluated. " /// We could evaluate the minimal disseminated disease of NPM-ALK positive ALCL patients by screening the NPM-ALK fusion gene in BM and PB by RT-PCR. /// 86.7% patients had a concordant results of NPM-ALK expression in PB and BM. /// "Patients with a positive NPM-ALK expression in BM had a 3-years EFS of (35.6??18.6)%, compared with (91.7??8.0)% for patients with negative NPM-ALK (P=0.038). "
NPM_ALK- 23678368breast cancer PCR - plasma cfDNA levels obtained at diagnosis in 201 paediatric lymphoma patients [43 Hodgkin lymphomas (HL), 45 anaplastic large cell lymphomas (ALCL), 88 Burkitt lymphomas (BL), 17 lymphoblastic (LBL), 8 diffuse large B cell lymphoma (DLBCL)] and 15 healthy individuals were determined using a quantitative PCR assay for POLR2 gene and, in addition, for NPM-ALK fusion gene in ALCL patients.
NPM_ALKt(2;5)(p23;q35) / t(2;17)(p23;q25) / t(2;11;2)(p23;p15;q31) / 12112524anaplastic large cell lymphoma;lymphoma - - While most of the ALK-positive ALCL (ALKomas) are characterized by the presence of the NPM-ALK fusion protein, the product of the t(2;5)(p23;q35), 10-20% of ALKomas contain variant ALK fusions, including ATIC-ALK, TFG-ALK, CLTC-ALK (previously designated CLTCL-ALK), TMP3-ALK, and MSN-ALK.
NPM_ALKt(2;5)(p23;q35) / 11704868anaplastic large cell lymphoma;lymphoma - - Anaplastic large cell lymphomas (ALCLs) are frequently associated with the t(2;5)(p23;q35) translocation, leading to the expression of NPM-ALK, a fusion protein linking nucleophosmin and anaplastic lymphoma kinase, a receptor tyrosine kinase. /// "As in ALCLs, NPM-ALK was expressed as a constitutively kinase-active 80 kDa protein, and could be detected by immunocytochemistry in nucleoli, nuclei and cytoplasm. " /// "In ALCLs, dimerization of NPM-ALK leads to constitutive autophosphorylation and activation of the kinase, necessary for NPM-ALK oncogenicity. " /// "To investigate whether NPM-ALK, like other oncogenic tyrosine kinases, can inhibit drug-induced apoptosis, we permanently transfected NPM-ALK into Jurkat T-cells. " /// These results suggest that the NPM-ALK antiapoptotic and mitogenic pathways are distinct.. /// "Expression of the oncogenic NPM-ALK chimeric protein in human lymphoid T-cells inhibits drug-induced, but not Fas-induced apoptosis.. "
NPM_ALKt(2;5)(p23;q35) / 26220634anaplastic large cell lymphoma - - The t(2;5)(p23;q35) chromosomal translocation results in the expression of the fusion protein NPM/ALK that when expressed in T-lymphocytes gives rise to anaplastic large cell lymphomas (ALCL). /// "Neurolenin B specifically decreased pro-carcinogenic NPM/ALK expression in ALK+ ALCL cells and, via the inhibition of NF-kB signalling, attenuated tumour intra/extravasation into the lymphatics. " /// ex Cass was shown to inhibit NPM/ALK expression. /// ex Cass inhibits NPM/ALK-driven cell expansion and NF-?B-driven tumour intravasation.. /// "In vitro treatment of ALCL by neurolenin B suppressed NPM/ALK, JunB and PDGF-R? expression, inhibited the growth of ALCL cells late in M phase, and induced apoptosis via caspase 3 without compromising mitochondrial activity (as a measure of general exogenic toxicity). "
NPM_ALKt(2;5) / t(2;5)(p23;q35) / 25820993anaplastic large cell lymphoma;non Hodgkin lymphoma;lymphoma - - About half of ALCL patients bear the t(2;5)(p23;q35) translocation, which results in the formation of the nucleophosmin-anaplastic lymphoma tyrosine kinase (NPM-ALK) fusion protein (ALCL ALK(+)).
NPM_ALKt(2;5) / t(2;5) / 9616164cutaneous T cell lymphoma;mycosis fungoides PCR;RT-PCR - Amplification of chromosomal breakpoints on both derivative chromosomes could represent an alternative to conventional cytogenetics for the diagnosis of t(2;5) and seems to be more reliable than the detection of cryptic NPM-ALK transcripts by nested RT-PCR.. /// " NPM-ALK chimeric transcripts, encoded by the t(2;5), lead to an aberrant expression of ALK by CD30+ systemic lymphomas. " /// "However, the expression of NPM-ALK transcripts was not associated with ALK1 immunoreactivity in MF, LyP, or BID cases. " /// "NPM-ALK transcripts were detected by nested reverse transcription-polymerase chain reaction (RT-PCR) in 1 of 11 lymphomatoid papulosis (LyP), 7 of 15 CD30+ primary cutaneous T-cell lymphoma (CTCL), 3 of 11 CD30+ secondary cutaneous lymphoma, 6 of 27 MF, and 1 of 16 BID. " /// "These cases, except for 1 secondary cutaneous lymphoma, were also characterized by reciprocal breakpoints on derivative chromosome 2, leading to the expression of reciprocal ALK-NPM transcripts. "
NPM_ALKt(2;5) / 16103750anaplastic large cell lymphoma;lymphoma - - NPM-ALK, an aberrant fusion protein produced from t(2;5) translocation in anaplastic large cell lymphoma (ALCL), fuses the N-terminus of B23 to the intracellular tyrosine kinase domain of ALK, provoking lymphomas by stimulating various mitogenic proteins including PI 3-kinase and PLC-gamma1.
NPM_ALKt(2;5)(p23;q35) / t(2;5) / 10725869anaplastic large cell lymphoma;lymphoma - - A subset of ALCL as presently defined is characterized by a balanced translocation, t(2;5)(p23;q35), resulting in a novel fusion protein (NPM-ALK) that can be readily detected by immunohistochemical methods using antibodies against the ALK protein.
NPM_ALKt(2;5) / 24616538anaplastic large cell lymphoma;lymphoma - - The NPM-ALK fusion protein is found in ALK(+) anaplastic large cell lymphomas harboring the t(2;5) chromosomal translocation.
NPM_ALK- 19131589anaplastic large cell lymphoma;lymphoma - - Proteome-wide identification of novel binding partners to the oncogenic fusion gene protein, NPM-ALK, using tandem affinity purification and mass spectrometry.. /// We believe that these data highlight the functional diversity of NPM-ALK and provide new research directions for the study of the biology of this oncoprotein.. /// "We also identified proteins that are involved in various cellular processes that were not previously described in association with NPM-ALK, such as MCM6 and MSH2 (DNA repair), Nup98 and importin 8 (subcellular protein transport), Stim1 (calcium signaling), 82Fip (RNA regulation), and BAG2 (proteosome degradation). " /// The NPM-ALK gene was cloned into an HB-tagged vector and expressed in GP293 cells.
NPM_ALKt(2;5) / t(2;5) / 16982741anaplastic large cell lymphoma;T cell lymphoma;non Hodgkin lymphoma;lymphoma - - In this study, we used the RNA interference method to modulate NPM-ALK protein expression in ALCL-derived, t(2;5)-positive Karpas 299 cells. /// We observed decreased CD30 expression when NPM-ALK was repressed. /// "Because aberrant CD30 expression was also observed in the T-cell lymphoma derived from lineage-specific NPM-ALK transgenic mice, we tested the hypothesis that there might be a functional relationship between the two neoplastic-related proteins: NPM-ALK and CD30. " /// "Combination of NPM-ALK repression and CD30 ligand leads to significantly increased tumor cell growth inhibition compared with one method alone, suggesting its potential application for ALCL-specific cancer treatment.. "
NPM_ALKt(2;5)(p23;q35) / t(2;5) / 14576483anaplastic large cell lymphoma;B cell lymphoma;lymphoma - - Anaplastic large cell lymphomas are associated with the t(2;5)(p23;q35) chromosome translocation in 40% to 60% of cases, leading to a new chimeric gene NPM-ALK. /// NPM-ALK positive lymphomas are generally reported to be of either T cell or null phenotype.
NPM_ALKt(2;5) / 25869285anaplastic large cell lymphoma - - Anaplastic lymphoma kinase-positive (ALK+) ALCL is associated with the NPM-ALK t(2;5) translocation, which is highly correlated with the identification of the ALK protein by immunohistochemistry.
NPM_ALK- 9885226anaplastic large cell lymphoma;lymphoma - - In anaplastic large-cell lymphoma (ALCL), the (2;5) chromosomal translocation creates a fusion gene encoding the 80-kD NPM-ALK hybrid protein. /// Immunocytochemical labeling with these antibodies can therefore confirm that an ALK-positive lymphoma expresses NPM-ALK (rather than a variant ALK-fusion protein) and may also provide evidence for chromosomal anomalies involving the NPM gene other than the classical (2;5) translocation.. /// The third antibody recognizes the C-terminal portion (deleted in NPM-ALK) and reacts only with wild-type NPM. /// "In contrast to normal tissues, the two antibodies against the N-terminal portion of NPM labeled the cytoplasm of neoplastic cells, in four ALK-positive ALCL, reflecting their reactivity with NPM-ALK fusion protein, whereas the antibody to the C-terminal NPM epitope labeled only cell nuclei. "
NPM_ALKt(2;5)(p23;q35) / t(2;5) / 12115586neuroectodermal tumor - - The initial identification of the ALK gene, expressed as C-terminal part of the transforming fusion protein NPM-ALK in the t(2;5)(p23;q35) lymphoma-associated chromosomal translocation, revealed a novel receptor tyrosine kinase (RTK). /// "Furthermore, full length receptor expression is absent in cell lines of the hematopoietic system with the exception of t(2;5)-associated anaplastic large cell lymphomas lines (ALCL), which are known to express chimeric NPM-ALK mRNA. " /// "While the constitutive activation of chimeric NPM-ALK molecules could be shown, no evidence was found for induced or constitutively activated ALK receptors in neuroblastoma, melanoma or breast carcinoma cell lines. "
NPM_ALK- 18572809anaplastic large cell lymphoma;lymphoma - - Little is known about the clinical implications of subtypes of ALCL harboring each of the 7 fusion genes, especially those of variant fusion genes other than NPM-ALK.
NPM_ALKp23;q35 / 10741140anaplastic large cell lymphoma - - It is now beyond doubt that a significant proportion(64 to 84%) of the cases diagnosed as ALCL is closely associated with the expression of chimeric NPM-ALK protein activated by the (2;5) (p23;q35) chromosomal translocation, which can be detected by anti-p80NPM/ALK or ALK1 antibodies.
NPM_ALKp23;q35 / 17185414anaplastic large cell lymphoma;lymphoma - - Constitutive overexpression and activation of NPM-ALK fusion protein [t(2:5)(p23;q35)] is a key oncogenic event that drives the survival and proliferation of anaplastic large-cell lymphomas (ALCLs). /// "NVP-TAE684 also induced down-regulation of CD30 expression, suggesting that CD30 may be used as a biomarker of therapeutic NPM-ALK kinase activity inhibition.. " /// "Identification of NVP-TAE684, a potent, selective, and efficacious inhibitor of NPM-ALK.. " /// NVP-TAE684 treatment resulted in a rapid and sustained inhibition of phosphorylation of NPM-ALK and its downstream effectors and subsequent induction of apoptosis and cell cycle arrest.
NPM_ALKt(2;5)(p23;q35) / t(2;5) / 9187427anaplastic large cell lymphoma - - We conclude that the majority of pediatric CD30+ ALCLs show ALK overexpression, consistent with the presence of the t(2;5)-encoded NPM-ALK fusion, but that the clinical significance of this entity remains unproven.. /// "A polyclonal antibody against residues of the kinase portion of NPM-ALK (designated anti-ALK 11) was tested for clinical utility in paraffin sections of 44 cases of pediatric large-cell lymphoma (LCL) and 17 additional lymphoma cases, by streptavidin-biotin-alkaline phosphatase method. "
NPM_ALKt(2;5)(p23;q35) / 19423729T cell lymphoma;anaplastic large cell lymphoma;lymphoma - - Approximately 85% of ALK(+) ALCL cases harbor the translocation t(2;5)(p23;q35), which generates the chimeric oncogene NPM-ALK. /// IGF-IR tyrosine kinase interacts with NPM-ALK oncogene to induce survival of T-cell ALK+ anaplastic large-cell lymphoma cells.. /// Our findings improve current understanding of the biology of IGF-IR and NPM-ALK and have significant therapeutic implications as they identify IGF-IR signaling as a potential therapeutic target in ALK(+) ALCL and possibly other types of malignant lymphoma.. /// "Importantly, we identified novel reciprocal functional interactions between IGF-IR and NPM-ALK. "
NPM_ALKt(2;5)(p23;q35) / 11891807anaplastic large cell lymphoma;lymphoma - - The t(2;5)(p23;q35) translocation results in the formation of a unique chimeric NPM-ALK protein (p80). /// CD30 and the NPM-ALK fusion protein (p80) are differentially expressed between peripheral blood and bone marrow in primary small cell variant of anaplastic large cell lymphoma..
NPM_ALKt(2;5)(p23;q35) / 26476082T cell lymphoma;lymphoma - - The expression of NPM-ALK chimeric oncogene results from the chromosomal translocation t(2;5)(p23;q35) that causes the fusion of the ALK and NPM genes. /// "In addition, NPM-ALK is structurally associated with wild-type NPM to form NPM/NPM-ALK heterodimers, which can translocate to the nucleus. " /// This translocation generates the NPM-ALK protein tyrosine kinase that forms the constitutively activated NPM-ALK/NPM-ALK homodimers. /// "Herein, we found that the SUMOylation pathway is deregulated in NPM-ALK(+) T-cell lymphoma cell lines and primary lymphoma tumors from patients. " /// "One possible mechanism for the SENP1-mediated decrease in NPM-ALK levels was the increase in NPM-ALK association with ubiquitin, which facilitates its degradation. " /// Our findings propose a model in which aberrancies in SUMOylation contribute to the pathogenesis of NPM-ALK(+) T-cell lymphoma. /// Nucleophosmin-anaplastic lymphoma kinase-expressing (NPM-ALK(+)) T-cell lymphoma is an aggressive form of cancer that commonly affects children and adolescents. /// We also identified Lys(24) and Lys(32) within the NPM domain as the sites where NPM-ALK conjugates with SUMO-1 and SUMO-3. /// The mechanisms that sustain the stability of NPM-ALK are not fully understood. /// SUMOylation Confers Posttranslational Stability on NPM-ALK Oncogenic Protein.. /// "Importantly, antagonizing SUMOylation by the SENP1 protease decreased the accumulation of NPM-ALK and suppressed lymphoma cell viability, proliferation, and anchorage-independent colony formation. "
NPM_ALKt(2;5) / 10980638anaplastic large cell lymphoma;lymphoma - - This pattern, never observed in normal lymphocytes, corresponds to the presence of the product of the hybrid gene NPM/ALK produced by t(2;5).
NPM_ALKt(3;5) / t(5;17) / t(2;5) / 9328447acute myeloid leukemia;myeloid leukemia;myelodysplastic syndrome;leukemia - - Three reciprocal chromosome translocations found in certain cases of leukemia/lymphoma involve fusions with the NPM/B23 gene, t(5;17) NPM-RARalpha, t(2;5) NPM-ALK, and the t(3;5) NPM-MLF1. /// "In the current study, MNDA was not able to bind the NPM-ALK chimera originating from the t(2;5) and containing residues 1-117 of NPM. " /// The additional 58 amino acids (amino acids 117-175) of the NPM sequence that are contained in the product of the NPM-MLF1 fusion gene relative to the product of the NPM-ALK fusion appear responsible for MNDA binding.
NPM_ALKt(2;5)(p23;q35) / t(2;5) / 10793082anaplastic large cell lymphoma;neuroblastoma;lymphoma - - ALK (anaplastic lymphoma kinase) is a tyrosine kinase receptor, expressed as part of the chimeric NPM-ALK protein, in anaplastic large cell lymphomas (ALCLs) exhibiting the t(2;5)(p23;q35) translocation.
NPM_ALKt(14;19)(q32;q13) / t(2;5)(p23;q35) / t(2;5) / t(14;19) / 16533741anaplastic large cell lymphoma;chronic lymphocytic leukemia;non Hodgkin lymphoma;leukemia;lymphoma - - Future studies should identify the relationships among the 3 independent molecules (ie, NPM/ALK, CD30, and Bcl-3) that are activated in t(2;5)+ ALCL.. /// "Anaplastic large cell lymphoma (ALCL) is a subtype of aggressive non-Hodgkin's lymphoma that is characterized by expression of CD30 and the NPM/ALK chimeric protein, which is generated by t(2;5)(p23;q35). "
NPM_ALKt(2;5) / 12401829anaplastic large cell lymphoma;lymphoma;lymphoproliferative disorder - - The NPM-ALK fusion transcript associated with the t(2;5) translocation was detected by reverse transcription polymerase chain reaction.
NPM_ALKt(2;5)(p23;q35) / 9736036anaplastic large cell lymphoma;T cell lymphoma;lymphoma - - The t(2;5)(p23;q35) translocation associated with CD30-positive anaplastic large cell lymphoma results in the production of a NPM-ALK chimeric protein, consisting of the N-terminal portion of the NPM protein joined to the entire cytoplasmic domain of the neural receptor tyrosine kinase ALK. /// "These findings, which have not been previously emphasized, strongly suggest that the neoplastic lesion (the NPM-ALK gene) must be present both in the large anaplastic and small tumor cells, and that ALK-positive lymphomas lie on a spectrum, their position being defined by the ratio of small to large neoplastic cells. "
NPM_ALKt(2;5)(p23;q35) / 10842190anaplastic large cell lymphoma;lymphoma - - A variable fraction of anaplastic large-cell lymphomas (ALCLs) exhibits a t(2;5)(p23;q35) translocation that results in expression of the chimeric hyperphosphorylated protein NPM-ALK (p80).
NPM_ALKt(2;5) / t(2;5) (p23;q35) / t(2;5) / 9449486anaplastic large cell lymphoma;lymphoma;lymphoproliferative disorder PCR;RT-PCR - The t(2;5)-associated p80 NPM/ALK fusion protein in nodal and cutaneous CD30+ lymphoproliferative disorders.. /// " A high percentage of extracutaneous CD30+ anaplastic large cell lymphomas (nodal ALCL) carry a specific chromosomal translocation, t(2;5) (p23;q35), that results in abnormal expression of p80 NPM/ALK chimeric protein (p80). " /// "In this exceptional cutaneous lesion, although we did not find NPM/ALK by RT-PCR, we detected strong expression of ALK using ALK1. "
NPM_ALKt(2;5)(p23;q35) / t(2;5) / 23666701anaplastic large cell lymphoma;lymphoma PCR - We describe a long-range nested PCR assay to detect NPM/ALK gene rearrangements.. /// "NPM/ALK, as well as ALK activation via other molecular abnormalities, plays an important role in the pathogenesis of ALCL. "
NPM_ALKt(2;5) / t(2;5) / 8562933anaplastic large cell lymphoma;lymphoma PCR;RT-PCR - NPM-ALK gene rearrangements were detected in all RT-PCR, NPM-ALK-positive ALCL by Southern blot analysis. /// "To investigate the presence and the precise frequency of NPM-ALK gene products among ALCL and HD cases, a large and well-characterized panel of ALCL (n = 49) and HD (n = 72) cases was studied using multiple strategies including reverse transcriptase-polymerase chain reaction (RT-PCR), Southern blot analysis, and immunohistochemistry. " /// "Overall, 6 (3 T and 3 null) of 49 ALCL and 3 (2 nodular sclerosis and 1 mixed cellularity) of 72 HD showed the presence of NPM-ALK transcripts by RT-PCR. " /// "Our data show that NPM-ALK gene transcripts are identified in a subpopulation of ALCL, almost exclusively in T or null cell in origin, and in rare cases of HD. "
NPM_ALKt(2;5)(p32;q35) / 19531656anaplastic large cell lymphoma;lymphoma - - Constitutive expression of the chimeric NPM/ALK fusion protein encoded by the t(2;5)(p32;q35) is a key oncogenic event in the pathogenesis of most anaplastic large cell lymphomas (ALCLs). /// A subset of the proteins distinguished NPM/ALK-positive ALCLs from NPM/ALK-negative ALCLs and Hodgkin lymphoma. /// The multiple NPM/ALK-deregulated pathways identified by MS analysis also predicted novel biologic effects of NPM/ALK expression. /// MS-based findings were confirmed using Western blotting and/or immunostaining of NPM/ALK-transfected cells and ALK-deregulated lymphomas. /// The proteomic signature of NPM/ALK reveals deregulation of multiple cellular pathways.. /// "In this regard, we showed loss of cell adhesion as a consequence of NPM/ALK expression in a kinase-dependent manner, and sensitivity of NPM/ALK-positive ALCLs to inhibition of the RAS, p42/44ERK, and FRAP/mTOR signaling pathways. " /// "These findings reveal that the NPM/ALK alteration affects diverse cellular pathways, and provide novel insights into NPM/ALK-positive ALCL pathobiology. " /// "Using a mass spectrometry (MS)-driven approach to identify changes in protein expression caused by the NPM/ALK fusion, we identified diverse NPM/ALK-induced changes affecting cell proliferation, ribosome synthesis, survival, apoptosis evasion, angiogenesis, and cytoarchitectural organization. "
NPM_ALKt(2;5)(p23;q35) / t(2;5) / t(2;5) / 7780128non Hodgkin lymphoma;anaplastic large cell lymphoma;lymphoma PCR;RT-PCR - To better define the spectrum of lymphomas that contain this translocation, we have analyzed 70 cases of non-Hodgkin's lymphoma (NHL) for expression of the t(2;5)-derived NPM/ALK chimeric message by reverse transcriptase-polymerase chain reaction (RT-PCR). /// "Using a previously described set of oligonucleotide primers, NPM/ALK chimeric transcripts were detected in 21 of 22 cases that contained the t(2;5) by cytogenetic analysis and in 10 of 48 cases that either lacked evidence of the t(2;5) or had unsuccessful cytogenetics. " /// "The NPM/ALK-expressing cases were not confined to NHLs with anaplastic morphology and included 15 ALCLs, 6 immunoblastic lymphomas, and 10 diffuse large-cell lymphomas. " /// "In all but 1 case, the NPM/ALK PCR products were of identical size and sequence, suggesting that the genomic chromosome breaks are clustered in a single intron in both NPM and ALK. " /// "Moreover, only slightly greater than half of the cases with anaplastic morphology and 59% of CD30-expressing cases were NPM/ALK positive. "
NPM_ALK- 17464320anaplastic large cell lymphoma;lymphoma PCR;RT-PCR - In this study, we developed three assays, all of which can be used with archival formalin-fixed, paraffin-embedded tissues: (1) a sensitive reverse transcription-polymerase chain reaction (RT-PCR) assay for various X-ALK fusion genes, (2) a 5' rapid amplification of cDNA ends (RACE) assay to identify unknown fusion partners, and (3) a real-time RT-PCR assay to quantify the amount of the NPM-ALK fusion transcript. /// Prognostic significance of NPM-ALK fusion transcript overexpression in ALK-positive anaplastic large-cell lymphoma.. /// Overexpression of the NPM-ALK fusion transcript may be associated with a poor prognosis of the patients with ALK(+) anaplastic large-cell lymphomas.. /// Patients with NPM-ALK overexpression showed a significantly unfavorable overall survival compared with those with a low expression of this transcript. /// The real-time quantitative RT-PCR assay showed that the NPM-ALK transcript was over expressed in four of 20 quantifiable cases.
NPM_ALKt(2;5) / t(2;5) / 11957137anaplastic large cell lymphoma;anaplastic large cell lymphoma;lymphoma - - Anaplastic large cell lymphoma of T/null-cell type (ALCL) is associated with a characteristic genetic abnormality t(2;5) that results in the NPM-ALK chimeric gene and the protein product derived thereof.
NPM_ALKt(2;5)(p23;q25) / t(2;5) / 17612934anaplastic large cell lymphoma;anaplastic large cell lymphoma;lymphoma - - Our data also suggested that the repression of the fusion gene might be a potential novel therapeutic strategy for NPM-ALK positive ALCLs.. /// These results revealed the importance of continuous expression of NPM-ALK in maintaining the growth of ALCL cells. /// Further study demonstrated that the downregulation of NPM-ALK resulted in decreased cell proliferation and increased cell apoptosis. /// Downregulation of NPM-ALK by siRNA causes anaplastic large cell lymphoma cell growth inhibition and augments the anti cancer effects of chemotherapy in vitro.. /// "To examine if the NPM-ALK is a potential therapeutic target in ALCL, we used siRNA to specifically downregulate the expression of the NPM-ALK in ALCL cell lines. " /// "When used in combination with chemotherapeutic agents, such as doxorubicin, the inhibition of the NPM-ALK augments the chemosensitivity of the tumor cells. " /// NPM-ALK is a constitutively activated kinase that transforms cells through stimulating several mitogenic signaling pathways.
NPM_ALKt(2;5)(p23;q35) / 9209648Hodgkin lymphoma PCR;RT-PCR - These data indicate that NPM/ALK fusion transcripts do not play an early role in the pathogenesis of HD. /// Whether the rare expression of NPM/ALK is the result of clonal heterogeneity or an indication for clonal evolution and progression toward ALCL can only be answered by the repeated analysis of indicator cases during the course of the disease.. /// "Since some cases of Hodgkin's disease (HD) and ALCL share common features, a common pathogenesis has been proposed in a report of the expression of NPM/ALK fusion mRNA in 11/13 Hodgkin's lymphomas. " /// NPM/ALK fusion mRNA expression in Hodgkin and Reed-Sternberg cells is rare but does occur: results from single-cell cDNA analysis.. /// We approached this question by micro-manipulatory isolation of single Hodgkin and Reed-Sternberg (H-RS) cells and subsequent RT-PCR amplification of NPM/ALK fusion cDNA from these single cells. /// "In 4 out of 7 cases, NPM/ALK fusion cDNA was detected in the RNA from whole lymph node tissue. " /// "In 2 out of 9 cases, NPM/ALK fusion sequences were amplified from single H-RS cells, albeit in a very low frequency (< 5%). "
NPM_ALKt(2;5)(p23;q35) / 12816858non Hodgkin lymphoma;B cell lymphoma;lymphoma - - All of these reported tumors lacked the NPM-ALK fusion transcript. /// ALK-positive plasmablastic B-cell lymphoma with expression of the NPM-ALK fusion transcript: report of 2 cases.. /// Both were positive for NPM-ALK by reverse transcriptase-polymerase chain reaction. /// Here we describe 2 well-characterized cases of ALK-positive B-cell lymphoma expressing the NPM-ALK fusion.
NPM_ALKt(2;5)(p23;q35) / 8866227anaplastic large cell lymphoma PCR;RT-PCR - Detection of the NPM-ALK genomic rearrangement of Ki-1 lymphoma and isolation of the involved NPM and ALK introns.. /// "Thus, we have shown that the introns involved by the NPM-ALK rearrangement seen in some Ki-1 lymphomas are relatively short, making the genomic rearrangement amenable to reliable detection by long-range DNA PCR. " /// "To examine the feasibility of long-range DNA PCR with the same exonic NPM and ALK primers for the detection of the genomic NPM-ALK rearrangement, we examined 20 cases of Ki-1 ALCL previously characterized by NPM-ALK RT-PCR. " /// Ten cases were positive for the NPM-ALK fusion RNA and 10 were negative. /// "We first confirmed that both the NPM and ALK normal introns are relatively short, approximately 1 and 2 kb, respectively, suggesting that the largest possible size for the chimeric NPM-ALK intron would be about 3 kb. "
NPM_ALKt(2;5)(p23;q35) / 8721682anaplastic large cell lymphoma;lymphoma PCR;RT-PCR - Molecular variant of the NPM-ALK rearrangement of Ki-1 lymphoma involving a cryptic ALK splice site.. /// "In the course of a survey of 15 cases of Ki-1 ALCL, we identified a single case with a slightly smaller NPM-ALK RT-PCR product, among 12 cases positive for this fusion RNA. " /// "Sequencing of this novel NPM-ALK RT-PCR product showed an in-frame junction of NPM to ALK, 30 bases distal to the usual ALK junction site, but at the usual NPM Junction site. "
NPM_ALKt(2;5)(p23;q35) / 10514417anaplastic large cell lymphoma;lymphoma - - Morphology, immunohistochemistry, and molecular genetics which demonstrated the NPM-ALK fusion protein, resulting from the t(2;5)(p23;q35), confirmed the identity of the xenograft with the original tumor.
NPM_ALK- 11561161anaplastic large cell lymphoma;rhabdomyosarcoma;neuroblastoma;sarcoma;lymphoma - - The immunocytochemical detection of NPM-ALK (and proteins encoded by other ALK fusion genes) has allowed the definition of a tumor entity, "ALK-positive lymphoma" (which shows only partial overlap with pathologists' diagnosis of ALCL), to be defined and is invaluable in distinguishing this disease from ALK-negative large cell lymphomas. /// "Biochemical studies suggest an anti-apoptotic function of NPM-ALK, and this may contribute to oncogenesis. "
NPM_ALK- 23598171non small cell lung cancer;anaplastic large cell lymphoma;small cell lu PCR;RT-PCR - We assessed ALK genomic status in tumour tissue and used quantitative RT-PCR to measure NPM-ALK fusion transcript in bone marrow and blood samples of patients with anaplastic large-cell lymphoma.
NPM_ALKt(2;5) / 17086210anaplastic large cell lymphoma;lymphoma - - Identification of multiple SNT-binding sites on NPM-ALK oncoprotein and their involvement in cell transformation.. /// NPM-ALK mutant protein mutated at these three binding sites showed significantly reduced transforming activity. /// "This raises a possibility that SNT family proteins play significant roles in cellular transformation triggered by NPM-ALK, which though remains to be verified.. " /// These observations indicate that the three SNT-binding sites of NPM-ALK are important for its transforming activity. /// Immunoprecipitation assay revealed that SNT-1 and SNT-2 interacted with NPM-ALK and kinase-negative NPM-ALK mutant. /// "Y156, Y567 and a 19-amino-acid sequence (aa 631-649) of NPM-ALK were essential for this interaction. "
NPM_ALKt(2;5)(p23;q35) / inv(2)(p21;p23) / 25727400non small cell lung cancer;anaplastic large cell lymphoma;small cell lu - - Activity of second-generation ALK inhibitors against crizotinib-resistant mutants in an NPM-ALK model compared to EML4-ALK..
NPM_ALKt(2;5) / t(2;5) (p23;q35) / t(2;5) / 7527617anaplastic large cell lymphoma;lymphoma PCR;RT-PCR - Using control samples, the sensitivity of the NPM-ALK RT-PCR assay was shown to be at least 1:10(4). /// "To determine if this tumor-specific genetic alteration also occurs in HD, we performed NPM-ALK RT-PCR on RNA samples extracted from 40 lymph node biopsies of HD (25 nodular sclerosis, 11 mixed cellularity, 2 lymphocyte depleted, 2 lymphocyte predominant). "
NPM_ALKt(2;5)(p23;q35) / t(2;5) / 10641597anaplastic large cell lymphoma;lymphoma - - About 40 to 50% of cases diagnosed as ALCL contain a specific chromosomal rearrangement, t(2;5)(p23;q35), resulting in expression of the chimeric tyrosine kinase NPM-ALK. /// "We conclude that NPM-ALK is not stimulated by CD30 activation, but exists as a constitutively hyperactivated protein. " /// We demonstrate that NPM-ALK specifically binds to the intracellular domain of the cytokine receptor CD30. /// "The tyrosine kinase NPM-ALK, associated with anaplastic large cell lymphoma, binds the intracellular domain of the surface receptor CD30 but is not activated by CD30 stimulation.. " /// Western blot analysis of coimmunoprecipitated CD30 and NPM-ALK proteins from stimulated Karpas 299 cells showed that the interaction of the proteins is not modified by stimulation. /// "To better elucidate the function of NPM-ALK, we investigated a possible mechanism for regulation of its activity. " /// In vitro binding assays revealed that the ALK portion of NPM-ALK mediates interaction of the two proteins. /// "Activation of CD30 neither enhanced NPM-ALK activity measured by autophosphorylation of the chimeric tyrosine kinase nor phosphorylation of phospholipase C-gamma, an NPM-ALK substrate. " /// Interaction with CD30 may extend the subcellular localization of NPM-ALK to the microenvironment of membrane-associated proteins..
NPM_ALKt(2;5) (p23;q35) / t(2;5)(p23;q35) / t(2;5) / 8781434anaplastic large cell lymphoma;non Hodgkin lymphoma;lymphoma PCR - Further studies are needed to determine the prognostic significance of the NPM-ALK rearrangement, to determine whether its detection can aid in the differential diagnosis between ALCL.
NPM_ALKp23;q21 / 10362790anaplastic large cell lymphoma;lymphoma - - The (2;5) translocation, found in many T-cell and null cell anaplastic large cell lymphomas (ALCLs), creates a hybrid gene encoding the 80-kd NPM-ALK protein. /// These results show how ALCL cases that express ALK proteins other than NPM-ALK can be detected by sensitive biochemical techniques using routine cryostat sections..
NPM_ALKt(2;5)(p23;q35) / t(2;5) / 16049513anaplastic large cell lymphoma;lymphoma PCR;RT-PCR - We studied 52 ALCL for NPM-ALK expression by RT-PCR: 47/52 biopsies were positive.
NPM_ALKt(2;5) / t(2;5) / 9517514anaplastic large cell lymphoma;lymphoma PCR;RT-PCR - Case two had a typical anaplastic large cell lymphoma (ALCL) morphology, with a suboptimal BM biopsy, but abnormal circulating cells in the PB showing the presence of the NPM/ALK fusion product demonstrated by RT-PCR.
NPM_ALKt(2;5)(p23;q35) / t(2;5) (p23;q35) / t(2;5) / 9274957anaplastic large cell lymphoma;T cell lymphoma;lymphoma PCR - Using primers spanning the NPM/ALK fusion junction, PCR amplification following reverse transcription (RT) of mRNA failed to show the products of NPM/ALK fusion in all samples tested.
NPM_ALKt(2;5)(p23;q35) / 14962911anaplastic large cell lymphoma;lymphoma - - In addition, transient expression of NPM-ALK in U-20S cells inhibited FOXO3a-mediated transactivation of reporter gene expression. /// "Thus, FOXO3a is a barrier to hematopoietic transformation that is overcome by phosphorylation and cytoplasmic relocalization induced by the expression of NPM-ALK.. " /// "To further study survival signaling by NPMALK, we generated Ba/F3 cell lines with either inducible or constitutive expression of NPM-ALK and examined the regulation of the AKT target FOXO3a. " /// "In Ba/F3 cells with induced or constitutive expression of NPM-ALK, concomitant AKT activation and phosphorylation of its substrate, FOXO3a, was observed. " /// NPM-ALK fusion kinase of anaplastic large-cell lymphoma regulates survival and proliferative signaling through modulation of FOXO3a..
NPM_ALKt(2;5)(p23;q35) / 16084951anaplastic large cell lymphoma;non Hodgkin lymphoma;lymphoma - - NPM-ALK has been shown to activate signal transducer and activator of transcription (STAT) 3, a transcriptional regulator of cyclin D3.
NPM_ALKt(2;5) / 12456315T cell lymphoma;non Hodgkin lymphoma;lymphoma - - Furthermore, identification of relevant protooncogenes and tumor suppressor genes involved in the pathogenesis of T-cell NHL such as the NPM/ALK fusion protein, p53, cyclin dependent kinase inhibitors (p15, p16, p21) and EBV as well as their interplay with the various regulatory pathways of cell cycle progression and apoptosis represent potential candidates for molecular-based therapy.
NPM_ALKp23;q35 / t(1;2)(q25;p23) / t(2;3)(p23;q21) / 10807789lymphoma - - We report here 2 lymphomas with an unusual finely granular cytoplasmic ALK staining pattern, clearly different from the pattern observed in ALK-positive lymphomas carrying NPM-ALK or its variants.
NPM_ALKt(2;5)(p23;q35) / 14563642anaplastic large cell lymphoma;lymphoma - - NPM-ALK possesses a constitutive tyrosine kinase activity responsible for its oncogenic property through activation of downstream effectors such as phospholipase C gamma (PLC-gamma) and the type IA phosphoinositide 3-kinase. /// "Overall, our data place Src-kinases as new important downstream effectors of NPM-ALK and as attractive potential therapeutic targets for new ALCL treatment.. " /// The kinase activity and the tyrosine 418 of NPM-ALK are required for its association with Src-kinases. /// "Moreover, using active or inactive forms of pp60(c-src) and NPM-ALK, we provide evidence that NPM-ALK is a potential substrate of pp60(c-src). " /// Y418F mutation of NPM-ALK impaired its association with Src-kinases and strongly reduced the proliferation rate of Ba/F3 cells. /// "Here, we show that the Src-kinases, particularly pp60(c-src), associate with and are activated by NPM-ALK expression in various cells, and in cell lines established from patients with ALCL. "
NPM_ALKt(2;5)(p23;q35) / 17519389anaplastic large cell lymphoma - - Several upstream modulators, cross-reacting oncogenes, and downstream effectors of NPM-ALK have been identified and characterized. /// "In this review, we briefly discuss ALCL and focus on NPM-ALK.. " /// "Only 13 years after the identification of NPM-ALK, tremendous progress has been made in our understanding of this molecule because of the relentless efforts of multiple investigators who have dissected its biologic roles using in vitro and in vivo experimental models. "
NPM_ALKt(2;5) / 12748172non Hodgkin lymphoma;anaplastic large cell lymphoma;lymphoma - - NPM-ALK is capable of transforming fibroblasts and lymphocytes in vitro and of causing lymphomas in mice. /// "In this study, we used an ALK fusion protein as bait in a yeast two-hybrid screen identifying NIPA (nuclear interacting partner of ALK) as a novel downstream target of NPM-ALK. "
NPM_ALKt(2;5) / 17537995anaplastic large cell lymphoma;lymphoma - - This study was aimed at identifying novel NPM/ALK-binding proteins that might contribute to its oncogenic transformation. /// Protein-protein interactions involving NPM/ALK are important for the activation of downstream signaling pathways. /// The interaction between NPM/ALK and PSF was dependent on an active ALK kinase domain and PSF was found to be tyrosine-phosphorylated in NPM/ALK-expressing cell lines and in primary ALK(+) ALCL samples. /// "Using a proteomic approach, several RNA/DNA-binding proteins were found to coimmunoprecipitate with NPM/ALK, including the multifunctional polypyrimidine tract binding proteinassociated splicing factor (PSF). " /// Y293F PSF was not phosphorylated by NPM/ALK and was not delocalized in NPM/ALK(+) cells. /// NPM/ALK binds and phosphorylates the RNA/DNA-binding protein PSF in anaplastic large-cell lymphoma.. /// "These results identify PSF as a novel NPM/ALK-binding protein and substrate, and suggest that PSF function may be perturbed in NPM/ALK-transformed cells.. " /// The expression of ALK fusion proteins induced delocalization of PSF from the nucleus to the cytoplasm and forced overexpression of PSF-inhibited proliferation and induced apoptosis in cells expressing NPM/ALK.
NPM_ALKt(2;5) / 20554525anaplastic large cell lymphoma;lymphoma - - Grb2 is an adaptor protein thought to play an important role in ALK-mediated transformation, but its interaction with NPM-ALK, as well as its function in regulating ALCL signaling pathways and cell growth, has never been elucidated. /// "Here we show that active NPM-ALK, but not a kinase-dead mutant, bound and induced Grb2 phosphorylation in tyrosine 160. " /// "Furthermore, Grb2 did not bind to a single region but rather to different regions of NPM-ALK, mainly Tyr(152-156), Tyr(567), and a proline-rich region, Pro(415-417). " /// The transforming activity mediated by NPM-ALK fusion induces different pathways that control proliferation and survival of lymphoma cells.
NPM_ALKt(2;5)(p23;q35) / 18070884anaplastic large cell lymphoma;lymphoma - - In contrast, mutation of the first and second (FFY), first and third (FYF), or all three (FFF) tyrosine residues impaired both kinase activity and transforming ability of NPM/ALK. /// "Because kinases are typically regulated by autophosphorylation of their activation loops, we systematically mutated (Tyr --> Phe) three potential autophosphorylation sites contained in the ""YXXXYY"" motif of the ALK activation loop, and determined the effect of these mutations on the catalytic activity and biological function of NPM/ALK. " /// "Together, our findings indicate that phosphorylation of the first tyrosine of the YXXXYY motif is necessary for the autoactivation of the ALK kinase domain and the transforming activity of NPM/ALK.. " /// Activated NPM/ALK stimulates downstream survival and proliferation signaling pathways leading to malignant transformation. /// We observed that mutation of both the second and third tyrosine residues (YFF mutant) did not affect the kinase activity or transforming ability of NPM/ALK. /// NPM/ALK is an oncogenic fusion protein expressed in approximately 50% of anaplastic large cell lymphoma cases.
NPM_ALKt(1;2)(q21;p23) / t(2;3)(p23;q21) / t(2;5)(p23;q35) / p23;q35 / 10381534anaplastic large cell lymphoma;lymphoma - - Moreover, ALK expression was confined to the cytoplasm of the tumor cells in each case, supporting the hypothesis that the observed nuclear localization of NPM-ALK in classical ALCL is not the site of oncogenic activity of the ALK kinase.. /// "These two cases were shown by an in vitro kinase assay to express ALK kinases (104 kD and 97 kD, respectively), which differed in size from the classical NPM-ALK fusion product (80 kD). "
NPM_ALKt(2;5) / 16105984anaplastic large cell lymphoma;lymphoma - - Finally, p130Cas-/- (also known as Bcar1-/-) fibroblasts expressing NPM-ALK showed impaired actin filament depolymerization and were no longer transformed compared with wild-type cells, indicating an essential role of p130Cas activation in ALK-mediated transformation.. /// "Along with transformation, NPM-ALK induces morphologic changes in fibroblasts and lymphoid cells, suggesting a direct role of ALK in cell shaping. " /// "In 293 cells and in fibroblasts as well as in human ALK-positive lymphoma cell lines, NPM-ALK was able to bind p130Cas and to induce its phosphorylation. " /// "Phosphorylation of p130Cas by NPM-ALK was partially independent from Src (tyrosine kinase pp60c-src) kinase activity, as it was still detectable in Syf-/- cells. " /// "Both of the effects were dependent on ALK kinase activity and on the adaptor protein growth factor receptor-bound protein 2 (Grb2), since no binding or phosphorylation was found with the kinase-dead mutant NPM-ALK(K210R) or in the presence of a Grb2 dominant-negative protein. " /// "In this study, we used a mass-spectrometry-based proteomic approach to search for proteins involved in cytoskeleton remodeling and identified p130Cas (p130 Crk-associated substrate) as a novel interactor of NPM-ALK. "
NPM_ALKt(2,5)(p23;q35) / / 21737449anaplastic large cell lymphoma;lymphoma - - Here, we show that PIKfyve associates with NPM-ALK and that the interaction involves the 181-300 region of the oncogene.
NPM_ALKt(2;5)(p23;q35) / 22852078anaplastic large cell lymphoma;B cell lymphoma;lymphoma - - NPM-ALK: The Prototypic Member of a Family of Oncogenic Fusion Tyrosine Kinases.. /// "Finally, using ALCL as an example, we will examine three key signalling pathways activated by NPM-ALK that contribute to proliferation and survival in ALCL.. " /// "The NPM-ALK fusion protein generated by this translocation is a constitutively active tyrosine kinase, and much research has focused on characterizing the signalling pathways and cellular activities this oncoprotein regulates in ALCL. "
NPM_ALKt(2;5) / 20454865anaplastic large cell lymphoma;lymphoma - - The NPM-ALK peptide interacts with the hydrophobic surface of the PTB domain and intermolecularly extends the PTB beta-sheet. /// "One of the interacting partners of NPM-ALK is the adaptor protein, Suc1-associated neurotrophic factor-induced tyrosine-phosphorylated target (SNT), and mutations that deprive NPM-ALK of all three of the SNT-binding sites significantly reduced the transforming activity. " /// "First, by isothermal titration calorimetry, we found that the phosphorylation-independent binding site in NPM-ALK interacts with the SNT-2 PTB domain more tightly than the phosphorylation-dependent binding sites. " /// "Second, the solution structure of the SNT-2 PTB domain in complex with the nonphosphorylated NPM-ALK peptide was determined by nuclear magnetic resonance spectroscopy. " /// "In this study, the interactions of the three binding sites in NPM-ALK with the phosphotyrosine binding (PTB) domain of SNT-2 were analyzed. "
NPM_ALKt(2;5)(p23;q35) / 16101126non Hodgkin lymphoma;anaplastic large cell lymphoma;lymphoma - - The transgenic approach described provides direct evidence for the strong transforming potential of NPM-ALK in T-cells and furthermore represents a system for the analysis of the oncogenic events mediated by NPM-ALK in vivo, which might be instrumental in the development of tyrosine kinase inhibitor therapies of potential clinical use.. /// Mice transgenic for NPM-ALK develop non-Hodgkin lymphomas.. /// The NPM-ALK chimeric protein is an activated tyrosine kinase that has been shown to be a potent oncogene and presumably plays a causative role in lymphomagenesis.
NPM_ALKt(2;5) / 11751994- - - These data indicate that NPM/ALK activates STAT3 and that PP2A and lack of protein inhibitor of activated STAT3 may be important in maintaining STAT3 in the activated state in the ALK+ TCL cells. /// Here we report that NPM/ALK induces continuous activation of STAT3. /// "Downstream effector molecules triggered by NPM/ALK remain, however, largely unidentified. " /// "Furthermore, STAT3 was constitutively associated with NPM/ALK in the ALK+ TCL cell lines. " /// Transfection of BaF3 cells with NPM/ALK resulted in tyrosine phosphorylation of STAT3.
NPM_ALKt(2;5) / t(2;5) / 11801565anaplastic large cell lymphoma;lymphoma - - The ALK domain of NPM-ALK contains kinase activity, which is responsible for the autophosphorylation of tyrosine residues of the oncogenic protein and phosphorylation of SH2-protein substrates. /// Model of inhibition of the NPM-ALK kinase activity by herbimycin A.. /// Our results show that herbimycin A interferes with NPM-ALK and Akt pathways in SUDHL-1 cells. /// "NPM-ALK, Akt, and pAkt were down-regulated after 24 h of incubation with herbimycin A. "
NPM_ALKt(2;5) / 17110082anaplastic large cell lymphoma;lymphoma - - Our results show that NPM-ALK mimics activated T-cell receptor signalling by inducing pathways associated with the activation of NFAT/AP-1 transcription factors that bind to promoter elements found in a broad array of cytokine genes.. /// "Specifically, NPM-ALK activates transcription from the TRE promoter element, an AP-1 binding region, an activity dependent on both Ras and Shc activity. " /// "This activity is dependent on NPM-ALK forming complexes with proteins that bind to autophosphorylated tyrosine residues at positions 156, 567 and 664, associated with binding to IRS-1, Shc and PLCgamma, respectively. " /// We show that NPM-ALK induces Ras activation and phosphorylation of the ERK MAP Kinase consistent with activation of the Ras-MAP Kinase pathway. /// "The NPM-ALK tyrosine kinase mimics TCR signalling pathways, inducing NFAT and AP-1 by RAS-dependent mechanisms.. "
NPM_ALKt(2;5) / 18089725anaplastic large cell lymphoma;lymphoma - - In addition, inhibition of key NPM-ALK signaling mediators, including phospholipase C-gamma, signal transducers and activators of transcription 3, extracellular signal-regulated kinases, and Akt by PF-2341066 were observed at concentrations or dose levels, which correlated with inhibition of NPM-ALK phosphorylation and function. /// "PF-2341066 also potently inhibited NPM-ALK phosphorylation in Karpas299 or SU-DHL-1 ALCL cells (mean IC(50) value, 24 nmol/L). " /// "Collectively, these data illustrate the potential clinical utility of inhibitors of NPM-ALK in treatment of patients with ALK-positive ALCL.. " /// A strong correlation was observed between antitumor response and inhibition of NPM-ALK phosphorylation and induction of apoptosis in tumor tissue. /// "bioavailable, small-molecule inhibitor of the catalytic activity of c-Met kinase and the NPM-ALK fusion protein. "
NPM_ALKt(2;5) / 12691918anaplastic large cell lymphoma;lymphoma - - Stat5-dependent transcriptional activity was inhibited by transfection of NPM/ALK-transformed cells with a dominant-negative Jak2 expression construct or treatment with AG490. /// We investigated the role of Jak2 in the context of NPM/ALK-mediated oncogenesis. /// NPM/ALK-transformed cells were treated with the Jak2 inhibitor AG490 or transfected with wild-type or dominant-negative Jak2 expression constructs to measure 3[H]-thymidine incorporation. /// "Also, NPM/ALK was present in immunoprecipitates of Jak2. " /// Jak2 was found to be constitutively tyrosine phosphorylated in ALCL cells and in NPM/ALK-transformed hematopoietic cells. /// Constitutive activation of Jak2 contributes to proliferation and resistance to apoptosis in NPM/ALK-transformed cells.. /// "Constitutive activation of Jak2 constitutes a pro-proliferative, anti-apoptotic signaling pathway in NPM/ALK-transformed hematopoietic cells.. " /// Inhibition of Jak2 led to a reduction of NPM/ALK-mediated proliferation and induced apoptosis. /// NPM/ALK exerts its transforming potential via activation of multiple signaling pathways promoting growth factor independence and protection from apoptosis.
NPM_ALKt(2;5) / 20015877anaplastic large cell lymphoma;lymphoma - - These findings reveal the convergence of STAT3 and ERK1/2 signaling pathways activated by NPM-ALK in mediating the regulation of C/EBPbeta expression, a transcription factor central to NPM-ALK transformation.. /// "Recently, we reported the abnormal expression of the transcription factor CCAAT/enhancer binding protein-beta (C/EBPbeta) in ALK-positive anaplastic large cell lymphomas, and demonstrated its dependence on NPM-ALK activity. "
NPM_ALKt(2;5)(p23;q35) / t(2;5) (p23;q35) / t(2;5) / t(2;5) / 9844824anaplastic large cell lymphoma;lymphoma PCR - We have previously developed a long-range genomic DNA-PCR assay to amplify the genomic NPM-ALK break points.
NPM_ALKt(2;5) / p23;q35 / 26709646anaplastic large cell lymphoma;lymphoma - - resulting in expression of NPM-ALK oncogenic kinase, which is capable of activating multiple oncogenic pathways.
NPM_ALKt(2;5)(p23;q35) / 15374880anaplastic large cell lymphoma;lymphoma - - Previously, NPM-ALK had been shown to activate the phosphatidylinositol 3 kinase (PI3K)/Akt pathway.
NPM_ALKt(2;5)(p23;q35) / 22179823anaplastic large cell lymphoma;T cell lymphoma;lymphoma - - NPM-ALK signals through glycogen synthase kinase 3? to promote oncogenesis.. /// Phosphorylation of pS(9)-GSK3? by NPM-ALK was mediated by the PI3K/AKT signaling pathway. /// Our results demonstrate that NPM-ALK regulates the phosphorylation of S(9)-GSK3? by PI3K/AKT. /// "Using a mass spectrometry-based phosphoproteomic screen, we identified GSK3? as a signaling mediator of NPM-ALK. " /// These findings provide support for the role of GSK3? as a mediator of NPM-ALK oncogenesis.. /// "Expression of NPM-ALK in 293T cells led to an increase of pS(9)-GSK3? (glycogen synthase kinase 3 beta) compared with kinase-defective K210R mutant NPM-ALK, but did not affect total GSK3? levels. " /// "NPM-ALK is a chimeric tyrosine kinase, which induces numerous signaling pathways that drive proliferation and abrogate apoptosis. "
NPM_ALKt(2;5)(p23;q35) / 19286999anaplastic large cell lymphoma;lymphoma - - NPM-ALK inhibits the p53 tumor suppressor pathway in an MDM2 and JNK-dependent manner..
NPM_ALK- 15214912anaplastic large cell lymphoma;lymphoma - - examining NPM-ALK translocation in each case with ALK expression should be useful to characterize the disease further..
NPM_ALKt(2;5)(p23;q35) / 17416736anaplastic large cell lymphoma;lymphoma - - We show that in 293T and Jurkat cells, forced expression of active NPM-ALK, but not kinase-dead mutant NPM-ALK (210K>R), induced JNK and cJun phosphorylation, and this was linked to a dramatic increase in AP-1 transcriptional activity. /// "cJun phosphorylation in NPM-ALK(+) ALCL cells is mediated by JNKs, as shown by selective knocking down of JNK1 and JNK2 genes using siRNA. " /// "Taken together, these findings reveal a novel function of NPM-ALK, phosphorylation and activation of JNK and cJun, which may contribute to uncontrolled cell-cycle progression and oncogenesis.. " /// NPM-ALK oncogenic kinase promotes cell-cycle progression through activation of JNK/cJun signaling in anaplastic large-cell lymphoma.. /// "Conversely, inhibition of ALK activity in NPM-ALK(+) ALCL cells resulted in a concentration-dependent dephosphorylation of JNK and cJun and decreased AP-1 DNA-binding. " /// "In addition, JNK physically binds NPM-ALK and is highly activated in cultured and primary NPM-ALK(+) ALCL cells. "
NPM_ALKt(2;5)(p23;q35) / p23;q35 / 10192426non Hodgkin Lymphoma - - Both large and small cells were reactive with antibody ALK1, which recognizes the chimaeric NPM-ALK protein associated with the t(2;5)(p23;q35).
NPM_ALK- 19451065anaplastic large cell lymphoma;lymphoma - - Our first patient was diagnosed shortly alter this entity was described based on morphology and Ki-1 positivity, while the diagnostic work-up for the last two children included accurate molecular diagnosis for ALK-NPM rearrangement.
NPM_ALK- 10450759- - - NPM/ALK rearrangements in indolent cutaneous lesions..
NPM_ALK- 15928040anaplastic large cell lymphoma;lymphoma - - Here we show that alphaDGK is constitutively activated in the NPM/ALK-positive ALCL-derived cell line Karpas 299 and in NPM/ALK-infected 32D hematopoietic cells.
NPM_ALK- 26018086anaplastic large cell lymphoma;non small cell lung cancer;lung cancer;lymphoma - - We confirmed these findings derived from human ALCL cells in murine pro-B cells that were transformed to cytokine independence by ectopic expression of an activated NPM-ALK fusion oncoprotein.
NPM_ALK- 26753883anaplastic large cell lymphoma;T cell lymphoma;lymphoma - - Here we present a model of peripheral ALCL pathogenesis where the malignancy is initiated in early thymocytes, before T-cell receptor (TCR) ?-rearrangement, which is bypassed in CD4/NPM-ALK transgenic mice following Notch1 expression.
NPM_ALK- 17611412anaplastic large cell lymphoma;lymphoma - - As such, in the absence of ligand, the ALK receptor is kinase inactive and its expression results in enhanced apoptosis, whereas kinase activation, due to a ligand or constitutive as in NPM-ALK, decreases apoptosis. /// " ALK (anaplastic lymphoma kinase) is a transmembrane receptor tyrosine kinase, initially discovered as part of the NPM-ALK fusion protein, resulting from a chromosomal rearrangement frequently associated with anaplastic large cell lymphomas. "
NPM_ALK- 25874976anaplastic large cell lymphoma - - ALK kinase domain mutations in primary anaplastic large cell lymphoma: consequences on NPM-ALK activity and sensitivity to tyrosine kinase inhibitors.. /// "Consistently, when co-expressed, INDELs increased crizotinib inhibitory activity on NPM-ALK signal processing, as demonstrated by the significant reduction of STAT3 phosphorylation. " /// "Therefore, these data suggest that NPM-ALK pre-therapeutic mutations may be found at low frequency in ALCL patients. " /// "INDELs, instead, generated kinase-dead variants with dominant negative effect on NPM-ALK kinase, in virtue of their capacity of forming non-functional heterocomplexes. " /// "In the present study, we analyzed ALK kinase domain mutational status of 36 paediatric ALCL patients at diagnosis to identify point mutations and gene aberrations that could impact on NPM-ALK gene expression, activity and sensitivity to small-molecule inhibitors. "
NPM_ALKt(2;5) / 11280786anaplastic large cell lymphoma;lymphoma - - NPM/ALK encodes a constitutively activated tyrosine kinase that belongs to the family of tyrosine kinases activated by chromosomal translocations. /// "In conclusion, our data indicate that NPM/ALK constitutively activates the PI3K-Akt pathway and that this pathway plays an important role in the NPM/ALK-mediated malignant transformation.. " /// "Finally, the Akt mutant (K179M) suppressed the tumorigenicity of NPM/ALK-transfected BaF3 cells injected into syngeneic mice. " /// "Both PI3K and Akt kinase were permanently activated in NPM/ALK-transfected BaF3 murine hematopoietic cells and in NPM/ALK-positive, but not in NPM/ALK-negative, patient-derived anaplastic large cell lymphoma cell lines. " /// PI3K was found in complex with NPM/ALK. /// "Our studies showed that NPM/ALK, similar to other members of this family, activates phosphatidylinositol 3-kinase (PI3K) and its downstream effector, serine/threonine kinase (Akt). "
NPM_ALK- 12024032non Hodgkin lymphoma;leukemia;lymphoma - - Fusion tyrosine kinases (FTKs) such as BCR/ABL, TEL/ABL, TEL/JAK2, TEL/PDGF beta R, TEL/TRKC(L), and NPM/ALK arise from reciprocal chromosomal translocations and cause acute and chronic leukemias and non-Hodgkin's lymphoma.
NPM_ALK- 26750252anaplastic large cell lymphoma;non small cell lung cancer;lung cancer;neuroblastoma;lymphoma - - Expression of ALK in normal human tissues is only found in a subset of neural cells, however it is involved in the genesis of several cancers through genetic aberrations involving translocation of the kinase domain with multiple fusion partners (e.g., NPM-ALK in anaplastic large cell lymphoma ALCL or EML4-ALK in non-small cell lung cancer) or activating mutations in the full-length receptor resulting in ligand-independent constitutive activation (e.g., neuroblastoma).
NPM_ALK- 21703420anaplastic large cell lymphoma;lymphoma - - Finally, NPM-ALK impeded the expected DNA damage-induced translocation of MSH2 out of the cytoplasm. /// "Using co-immunoprecipitation, we found that increasing levels of NPM-ALK expression in HEK293 cells resulted in decreased levels of MSH6 bound to MSH2, whereas MSH2??NPM-ALK binding was increased. " /// MSH2 was found to be tyrosine phosphorylated in the presence of NPM-ALK. /// "In this study, we found in vitro evidence that enforced expression of NPM-ALK in HEK293 cells suppressed MMR function. " /// "To conclude, our data support a model in which the suppression of MMR by NPM-ALK is attributed to its ability to interfere with normal MSH2 biochemistry and function.. " /// Fusion tyrosine kinase NPM-ALK Deregulates MSH2 and suppresses DNA mismatch repair function novel insights into a potent oncoprotein.. /// The fusion tyrosine kinase NPM-ALK is central to the pathogenesis of ALK-positive anaplastic large cell lymphoma (ALK(+)ALCL).
NPM_ALKt(2;5) / 11110708anaplastic large cell lymphoma;lymphoma - - Here, we show that NPM-ALK recruits the C-terminal SH2 domain of the phosphatidylinositol 3-kinase (PI 3kinase) p85 subunit. /// "Thus, NPM-ALK activates the antiapoptotic PI 3-kinase/Akt pathway, which likely contributes to the molecular pathogenesis of ALCL. " /// "Furthermore, apoptosis induced by overexpression of the proapoptotic molecule Bad could be partially blocked by the overexpression of NPM-ALK. " /// We have previously identified PLC-gamma as a crucial downstream signaling molecule of NPM-ALK that contributes to its mitogenic potential. /// Primary murine bone marrow retrovirally transduced with NPM-ALK showed a transformed phenotype that was reversible on treatment with PI 3-kinase inhibitors.
NPM_ALK- 16900211anaplastic large cell lymphoma;non Hodgkin Lymphoma - - The crucial role of NPM-ALK in the regulation of serpin A1 expression was further demonstrated by using both ectopic expression and downregulation, by RNA interference, of the NPM-ALK oncogene.
NPM_ALKt(2;5)(p23;q35) / 9021682anaplastic large cell lymphoma;non Hodgkin lymphoma;lymphoma - - Subsequent cDNA cloning showed p80 to be a fusion protein of two genes, the novel tyrosine kinase gene and the nucleophosmin gene, in accordance with the sequence of the NPM/ALK gene.
NPM_ALKt(2;5)(p23;q35) / t(2;5) / 9209450anaplastic large cell lymphoma;lymphoma - - Subsequent cDNA cloning revealed p80 to be a fusion protein of two genes, the novel tyrosine kinase gene and the nucleophosmin gene, in accordance with the sequence of the NPM/ALK gene (Morris et al.). /// "Subsequent cDNA cloning showed p80 to be a fusion protein of two genes, the novel tyrosine kinase gene and the nucleophosmin gene, in accordance with the sequence of the NPM/ALK gene (Morris et al, Science 263:1281, 1994). "
NPM_ALK- 7656205anaplastic large cell lymphoma;non Hodgkin lymphoma;lymphoma PCR;RT-PCR - In contrast, expression of a NPM/ALK chimeric gene was observed which was absent in the ET.
NPM_ALKt(2;5)(p23;q35) / t(2;5) / 15883821anaplastic large cell lymphoma;hematopoietic malignancy;lymphoma - - NPM-ALK activates the antiapoptotic phosphatidylinositol-3 kinase/Akt (PI3K/Akt) signaling pathway, which plays a critical role in cell survival and apoptosis.
NPM_ALK- 15184887anaplastic large cell lymphoma;lymphoma - - It has been shown that NPM-ALK binds to and activates signal transducer and activator of transcription 3 (STAT3) in vitro, and that STAT3 is constitutively active in ALK(+) ALCL cell lines and tumors.
NPM_ALK- 19131793anaplastic large cell lymphoma;lymphoma - - This finding was confirmed by reverse transcription-polymerase chain reaction analysis of the NPM/ALK fusion protein.
NPM_ALK- 18509351anaplastic large cell lymphoma;lymphoma - - To conclude, for the first time, we demonstrate the importance of the IL-22 autocrine pathway in a lymphoid malignancy, and reveal yet another novel function of NPM-ALK..
NPM_ALK- 21134980B cell lymphoma;lymphoma - - We examined an ALK-positive large B-cell lymphoma case showing an anti-ALK immunohistochemistry pattern distinct from those of 2 known ALK fusions, CLTC-ALK and NPM-ALK, for the presence of a novel ALK fusion.
NPM_ALKt(2;5)(p23;q35) / t(2;5) / 9450809anaplastic large cell lymphoma;non Hodgkin lymphoma;lymphoma PCR;RT-PCR - This finding was confirmed both by RT-PCR analysis of the NPM/ALK fusion protein and by positive staining with the p80(NPM/ALK) antibody.
NPM_ALK- 9777981lymphoma;lymphoproliferative disorder - - Nested reverse transcriptase-polymerase chain reaction allowed the detection of NPM-ALK transcripts in 10 of 26 CD30+ primary and in 3 of 11 secondary cutaneous large-cell lymphomas. /// "In CD30+ primary cutaneous lymphoproliferation, NPM-ALK transcripts might be expressed by very rare normal or tumoral cells that are undetectable by immunohistochemistry. " /// "However, the expression of either NPM-ALK transcripts or ALK-protein was not correlated with prognosis or age in CD30+ cutaneous lymphoproliferations.. "
NPM_ALKt(2;5)(p23;q35) / t(2;5) / 8701987lymphomatoid papulosis;non Hodgkin Lymphoma ISH - To identify cells carrying the t(2;5) translocation, we used immunohistochemistry to detect the ALK-encoded p80 protein and in situ hybridization for the specific detection of NPM-ALK transcripts. /// The t(2;5) generates a chimeric NPM-ALK transcript encoded by the nucleophosmin NPM gene fused to the anaplastic lymphoma kinase gene ALK. /// Both p80 protein and NPM-ALK transcripts were expressed by anaplastic or large CD30+ lymphoma cells with positive NPM-ALK amplification. /// Using a reverse transcriptase nested polymerase chain reaction assay we have detected NPM-ALK transcripts within CD30+ primary cutaneous lymphoma and lymphomatoid papulosis (LP).
NPM_ALKt(2;5)(p23;q35) / 11215285anaplastic large cell lymphoma;lymphoma - - Despite multiple copies of the normal ALK gene, immunohistochemical, reverse transcriptase polymerase chain reaction, and western blot analysis demonstrated that only the fusion gene NPM/ALK was expressed and that normal ALK genes remained silent. /// Anaplastic large cell lymphoma with the t(2;5)(p23;q35) NPM/ALK chromosomal translocation and duplication of the short arm of the non-translocated chromosome 2 involving the full length of the ALK gene..
NPM_ALKt(2;5)(p23;q35) / t(2;5) / 11607814non Hodgkin lymphoma;anaplastic large cell lymphoma;lymphoma - - Much confusion about the exact classification and clinicopathological features of this subgroup of NHL was clarified with the identification of NPM-ALK (nucleophosmin-anaplastic lymphoma kinase) as the oncogene created by the t(2;5) (Morris et al., 1994). /// "With the discovery of NPM-ALK as the specific lymphoma gene mutation, this NHL subtype could be redefined on the molecular level. "
NPM_ALKt(2;5) / t(2;5)(p23;q35) / t(2;5) / 9598798anaplastic large cell lymphoma;lymphoma ISH - Two extranodal lesions had NPM/ALK fusion transcripts detected by nested reverse transcriptase-polymerase chain reaction.
NPM_ALK- 14586401B cell lymphoma;anaplastic large cell lymphoma;lymphoma - - The NPM-ALK kinase is active in primary tumour tissue and forms a multimeric complex with tyrosine-phosphorylated proteins, that is, Shc. /// Lymphomas develop in two transgenic lines in which the Vav promoter regulates NPM-ALK expression. /// The new transgenic models provide a system for investigating the oncogenic events mediated by NPM-ALK in situ and a physiologically relevant context for developing tyrosine kinase inhibitor therapies of potential use in the clinic.. /// Vav-promoter regulated oncogenic fusion protein NPM-ALK in transgenic mice causes B-cell lymphomas with hyperactive Jun kinase..

ChimerSEQ

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The fusion gene pair NPM--ALK information is not available in CHIMERSEQ (CHIMERDB 3.0) database.

ChiTaRS 2.1

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The fusion gene pair NPM--ALK information is not available in CHITARS database.

FARE-CAFE

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The fusion gene pair NPM--ALK information is not available in FARE-CAFE.

TicDB

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The fusion gene pair NPM--ALK information is not available in TicDB.

TUMOR FUSION Gene Data Portal

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The fusion gene pair NPM--ALK information is not available in TUMOR FUSION Gene Data Portal.

FusionCancer

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The fusion gene pair NPM--ALK information is not available in FusionCancer Database.

ConjoinG

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The fusion gene pair NPM--ALK information is not available in ConjoinG Database.

1000Genome

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Fusion gene NPM--ALK has not been seen in a healthy sample (RNA-seq data from some samples from 1000 genomes project: Greger et al., Tandem RNA Chimeras Contribute to Transcriptome Diversity in Human Population and Are Associated with Intronic Genetic Variants, Plos One, Aug 2014 ). Therefore this candidate fusion gene has a low probability of being a false positive. [Fusion gene List compiled from FusionCatcher]

18Cancers

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Fusion gene NPM--ALK is not found in a RNA-seq dataset of 18 types of cancers from 600 tumor samples (B. Alaei-Mahabadia et al., Global analysis of somatic structural genomic alterations and their impact on gene expression in diverse human cancers, PNAS, Nov. 2016 )

Bodymap2

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Fusion gene NPM--ALK is not found in the list of known false positive fusion genes. The list has been generated from healthy human samples collected from 16 organs from Illumina BodyMap2 RNA-seq database. A candidate fusion gene found in this list has a very high probability of being a false positive. [Fusion gene List compiled from FusionCatcher]

HPA

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Fusion gene NPM--ALK is not found in a healthy sample (RNA-seq database of 27 healthy tissues from 95 human individuals). A candidate fusion gene found in this dataset has a very high probability of being a false positive. [Fusion gene List compiled from FusionCatcher]

Non_Tumor_Cells

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Fusion gene NPM--ALK was not found among the fusion genes which have been previously reported/found in non-tumor cell lines, like for example HEK293. The genes which are observed in those list can be considered as non-somatic mutation. [Fusion gene List compiled from FusionCatcher]

Babiceanu_Dataset

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The fusion gene pair NPM--ALK information is not available in Babiceanu_Dataset.

Banned_Dataset

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Fusion gene NPM--ALK is not found in the list of known false positive fusion genes. A candidate fusion gene found in this list has a very high probability of being a false positive. [Fusion gene List compiled from FusionCatcher]

Known_Fusions

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Fusion gene NPM--ALK has not been found in the list of fusions previously reported or published in scientific articles/reports/books/abstracts/databases, indexed by Google, Google Scholar, PubMed, etc. The list has been manually curated by FusionCatcher software. This label has only the role to answer with YES or NO the question "has ever before a given (candidate) fusion gene been published or reported?". This label does not have in anyway the role to provide the original references to the original scientific articles/reports/books/abstracts/databases for a given fusion gene.[Fusion gene List compiled from FusionCatcher]

ONGene Database

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The head gene NPM is a known oncogene according to ONGENE database.


The tail gene ALK is a known oncogene according to ONGENE database.

Bushman Cancer Gene Database

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The head gene NPM is cancer associated according to Bushman Cancer Gene database.


The tail gene ALK is cancer associated according to Bushman Cancer Gene database.

Tumor Gene Set By Uniprot

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The head gene NPM is not a proto-oncogene or tumor suppresor gene according to Uniprot database.


The tail gene ALK is proto-oncogene or tumor suppresor gene according to Uniprot database.

Oesophagus_Dataset

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Fusion gene NPM--ALK is not found in oesophageal tumors from TCGA samples, which are published here.

Gliomas_Dataset

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Fusion gene NPM--ALK is not found in the RNA-seq dataset of 272 glioblastomas, published here.

Prostate_Dataset

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The fusion gene pair NPM--ALK information is not available in Prostate Dataset (150 prostate tumor RNAs, Robison et al, Integrative Clinical Genomics of Advanced Prostate Cancer, Cell, Vol. 161, May 2015, http://dx.doi.org/10.1016/j.cell.2015.05.001).

Pancreases_Dataset

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Fusion gene NPM--ALK is not found in pancreatic tumor dataset, published here.

GTEx

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Fusion gene NPM--ALK has not been found in a healthy sample (GTEx database of healthy tissues (thru FusionAnnotator)). A candidate fusion gene found in this set has a very high probability of being a false positive. [Fusion gene List compiled from FusionCatcher]

Klijin_Dataset

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The fusion gene pair NPM--ALK information is not available in Klijn Dataset.

Fimereli_Dataset

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The fusion gene pair NPM--ALK information is not found in Fimereli_Dataset.

Literature

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The fusion gene pair NPM--ALK information is not found in known fusion genelist compiled from literature.

Cortex_Dataset

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Fusion gene NPM--ALK is not found in Cortex_Dataset (Fusion genes found in healthy human brains (BA9 prefrontal cortex)) . A candidate fusion gene found in this dataset has a very high probability of being a false positive.

ChromothripsisDB

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The fusion gene pair NPM--ALK information is not available in ChromothripsisDB database.