Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound   Target Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound

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Query: EC:2.7.10.1 (ERK)
95,504 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Three mouse genomic domains, Fim1, Fim2, and Fim3, were previously described as proviral integration regions frequently involved in the early stages of myeloblastic leukemogenesis induced in vivo or in vitro by the Friend murine leukemia virus. Fim2 was identified as the 5' end of the c-Fms protooncogene, which encodes the receptor of the macrophage colony stimulating factor (Csflr). The functions of Fim1 and Fim3 are not yet known, but these regions are highly conserved among different species. To examine whether these regions could correspond to known human loci involved in genetic alterations specific to some human leukemias, we undertook their chromosomal mapping. The localization of FIM2/c-FMS on 5q33 was confirmed. FIM1 and FIM3 were localized on human chromosomes 6p22.3-p23 and 3q27 respectively. Interestingly, translocations involving these two regions have been described in various hematopoietic malignancies: the t(6;9)(p23;q34) in acute nonlymphocytic leukemias and the 3q26-q28 translocations in a large variety of leukemias.
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PMID:The human homologues of Fim1, Fim2/c-Fms, and Fim3, three retroviral integration regions involved in mouse myeloblastic leukemias, are respectively located on chromosomes 6p23, 5q33, and 3q27. 292 Oct 36

Hodgkin's disease (HD) and Ki-1 positive anaplastic large cell lymphoma (Ki-1 ALCL) appear pathologically and immunohistochemically related, and a common histogenesis has been postulated in at least some cases. The breakpoints of the t(2;5) (p23;q35) [corrected] translocation, which is reported in about 40% of Ki-1 ALCL, have recently been cloned. They involve a novel tyrosine kinase gene, ALK, at 2p23 and the nucleophosmin gene, NPM, at 5q35. Reverse transcriptase polymerase chain reaction (RT-PCR) using NPM and ALK primers consistently detects a fusion product in Ki-1 ALCL cases with the translocation. 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). Using control samples, the sensitivity of the NPM-ALK RT-PCR assay was shown to be at least 1:10(4). Amplifiable template was confirmed in all samples by RT-PCR using beta-actin primers. None of the 40 cases showed the expected 177-bp RT-PCR product indicative of the translocation. We conclude that the most common primary genetic alteration in Ki-1 ALCL, the t(2;5), is absent or very infrequent in typical cases of HD. These results further support the concept that HD and Ki-1 ALCL are pathogenetically distinct entities.
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PMID:Reverse transcriptase polymerase chain reaction for the Ki-1 anaplastic large cell lymphoma-associated t(2;5) translocation in Hodgkin's disease. 752 17

An unusual hematologic neoplasia has been described recently in which the predominant clinical features include T-cell lymphoma, myeloid hyperplasia, and eosinophilia. The multilineage involvement in this disorder suggests transformation of a primitive stem cell. Abnormal karyotypes have been described in three such cases, including one case with t(8;13)(p11.2;q12) and a second case with t(8;13)(p23;q14). We report translocation of chromosomes 8 and 13 in lymph node karyotypes from two patients with this syndrome. Fluorescence in situ hybridization confirmed an identical translocation, t(8;13)(p11;q11-12), in lymphoma cells from each patient. The translocation breakpoints are of particular interest because the FLT3 receptor tyrosine kinase gene has been mapped 13q12. FLT3 is expressed highly in hematopoietic progenitor cells and in myeloid and lymphoid acute leukemias.
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PMID:Translocation t(8;13)(p11;q11-12) in stem cell leukemia/lymphoma of T-cell and myeloid lineages. 753 88

Anaplastic large cell lymphoma (ALCL) and Hodgkin's disease (HD) have some pathologic and immunohistochemical similarities, and a histogenetic relationship between them has been suggested by some investigators. By cytogenetic study, the t(2;5)(p23;q35) translocation appears to be unique for ALCL. The breakpoints of the t(2;5)(p23;q35) have recently been cloned and are reported to involve a novel tyrosine kinase gene, anaplastic lymphoma kinase (alk), on chromosome 2 and the nucleophosmin gene (npm) on chromosome 5. Therefore, we studied the frequency of npm-alk translocation in ALCL using a reverse transcriptase-polymerase chain reaction (RT-PCR) assay. We also studied HD and a variety of reactive lymphoid lesions since there is contradictory information in the literature on the occurrence of the npm-alk rearrangement in HD. We detected npm-alk hybrid mRNA in 8 of 22 cases of ALCL (36%), but none of the 21 cases of HD or the 11 cases with reactive lesions contained amplifiable template. All positive ALCL had the T or indeterminate phenotype and occurred in young adults or children. There was very good correlation between a cytogenetically detectable t(2;5) and a positive signal by RT-PCR. Our results indicate a selective but relatively infrequent association between the t(2;5) and ALCL of T or indeterminate phenotype, not shared with HD or reactive hyperplasia.
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PMID:Transcripts of the npm-alk fusion gene in anaplastic large cell lymphoma, Hodgkin's disease, and reactive lymphoid lesions. 757 58

The translocation t(2;5)(p23;q35), discovered in CD30+ anaplastic large cell (ALC) lymphomas, creates a potentially oncogenic fusion gene, part of which is contributed by a novel tyrosine kinase, ALK. Absence of ALK expression from normal hematolymphoid cells provides a basis for the morphologic assessment of t(2;5). The distribution of the t(2;5) in ALC lymphomas and Hodgkin's disease (HD), as assayed by nonmorphologic methods, is controversial. We used in situ hybridization and/or immunohistology to show ALK gene products in 85 ALC lymphomas, 82 HD cases, 40 other lymphoproliferations, as well as in 6 HD- and 4 ALC lymphoma-derived cell lines. ALK gene products were restricted to t(2;5)-positive ALC lymphoma cell lines and tumor cells of 16 primary non-B cell, common-type ALC lymphomas. These were mainly from young patients with initial lymphonodal disease. ALK expression was not detectable in any other specimen, including all cases of HD and HD-like type ALC lymphoma as well as secondary ALC lymphomas. Full congruence was noted for labeling results obtained with both methods. In agreement with cytogenetic analyses, but at variance with recently published studies, ALK gene expression distinguishes a subset of ALC lymphomas from other CD30+ lymphomas, including HD. The results do not support concepts attributing a significant role to the t(2;5) in the development of HD.
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PMID:ALK gene products in anaplastic large cell lymphomas and Hodgkin's disease. 765 1

The t(2;5)(p23;q35) translocation is associated with a high percentage of anaplastic large-cell lymphomas (ALCL) of T- or null-cell phenotype. This translocation was recently cloned and results in the fusion of the nucleophosmin gene (NPM) on chromosome 5q35 to a novel tyrosine kinase-encoding gene designated anaplastic lymphoma kinase (ALK) on chromosome 2p23. Using a sensitive and specific reverse transcription-polymerase chain reaction (RT-PCR) assay to detect the NPM/ALK fusion transcript, we assessed the involvement of NPM/ALK in a series of histologically and immunohistochemically confirmed ALCL, in non-ALCL aggressive non-Hodgkin's lymphomas of T-cell phenotype, and in Hodgkin's disease (HD) to better define the morphologic spectrum of disease associated with this translocation. Twenty-four cases of ALCL were selected on the basis of CD30 positivity and histologic features. Seventeen cases presented as classical nodal and extranodal disease, four cases presented as primary cutaneous disease, and three were associated with human immunodeficiency virus (HIV) infection. As ALCL may show overlapping histology with both HD and other aggressive non-Hodgkin's lymphomas, particularly of T-cell phenotype (T-NHL), we also studied 34 cases of HD and 19 of T-NHL. NPM/ALK chimeric transcripts of identical size were detected in 11 of the 24 (46%) cases of ALCL. NPM/ALK fusion transcripts were found in 11 of 17 (65%) classical ALCL cases but were not detected in the four primary cutaneous cases of ALCL or in the three HIV-related ALCL cases. In addition, NPM/ALK transcripts were not detected in any of the 34 cases of HD or in the 19 cases of T-NHL. These data indicate that NPM/ALK fusion transcripts occur in a high percentage of classical nodal ALCL (65%). In addition, these data strongly suggest that ALCL, as defined in this study, is not pathogenetically related to either HD disease or the majority of other types of aggressive T-NHL. This is a US government work. There are no restrictions on its use.
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PMID:Analysis of the t(2;5)(p23;q35) translocation by reverse transcription-polymerase chain reaction in CD30+ anaplastic large-cell lymphomas, in other non-Hodgkin's lymphomas of T-cell phenotype, and in Hodgkin's disease. 766 79

FLT4 is a recently cloned receptor tyrosine kinase cDNA, which is characterized by seven immunoglobulin-like loops in its extracellular domain. We have previously mapped the FLT4 gene to chromosome segment 5q33-qter using somatic cell hybrids. Here we have refined the localization to band 5q35 by fluorescence in situ hybridization and show that the gene is translocated to chromosomes 2 and 6 in the t(2;5)(p23;q35) and t(5;6)(q35;p21) translocations, respectively, of Ki-I-positive lymphomas, as well as to chromosome 3 in the t(3;5)(q25.1;q34) translocation, which is occasionally found in myelodysplastic syndromes and acute myeloid leukemia. No evidence was obtained for a rearrangement or deregulation of the translocated FLT4 gene. We further show that abundant FLT4 mRNA expression occurs only in erythroid and megakaryoblastoid cell lines among nine leukemia cell lines studied.
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PMID:FLT4 receptor tyrosine kinase gene mapping to chromosome band 5q35 in relation to the t(2;5), t(5;6), and t(3;5) translocations. 768 67

CD30 positive anaplastic large cell lymphoma (ALCL) is a type of non-Hodgkin's lymphoma associated with a specific chromosome translocation between chromosomes 2 and 5. Recent molecular characterization of the translocation breakpoint has identified a gene fusion between NPM (nucleophosmin) and ALK (anaplastic lymphoma kinase). Using a DNA hybridization technique, the NPM rearrangement was found among 5/5 ALCL samples. 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. The rapidity and robustness of this method may have diagnostic applications for ALCL.
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PMID:Detection of NPM-ALK DNA rearrangement in CD30 positive anaplastic large cell lymphoma. 777 31

The t(2;5)(p23;q35) translocation was initially identified in cases of anaplastic large-cell lymphoma (ALCL) that expressed the Ki-1 (CD30) antigen. We have recently cloned this translocation and shown it to encode a chimeric product consisting of the N-terminal portion of a nonribosomal nucleolar phosphoprotein, nucleophosmin (NPM), from chromosome 5, fused to the kinase domain of a novel transmembrane tyrosine-specific protein kinase, anaplastic lymphoma kinase (ALK), from chromosome 2. 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. 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. 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. Moreover, only slightly greater than half of the cases with anaplastic morphology and 59% of CD30-expressing cases were NPM/ALK positive. Thus, neither anaplastic morphology nor the expression of CD30 accurately predicted the presence of this molecular genetic subtype of lymphoma.
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PMID:Molecular detection of the (2;5) translocation of non-Hodgkin's lymphoma by reverse transcriptase-polymerase chain reaction. 778 Jan 28

Although cytogenetic data suggest that the t(2;5)-(p23;q35) translocation occurs in many cases of CD30+ lymphomas, the exact frequency of this event is still unknown. To clarify this issue and its epidemiological characteristics, we examined 37 formalin-fixed, paraffin-embedded specimens of CD30+ lymphomas from the United States and Hong Kong by reverse transcriptase-polymerase chain reaction (RT-PCR) for the status of the NPM and ALK genes, which are typically juxtaposed by the t(2;5) translocation. Thirty-four cases were classified as anaplastic large cell lymphomas (ALCL), 2 cases as non-anaplastic large cell lymphomas (LCL), and 1 case as the small cell variant of CD30+ lymphoma. The t(2;5) translocation was detected in 6 cases (16%), including 3 of 18 American patients and 3 of 19 cases from Hong Kong. All cases had a 185-bp NPM RT-PCR product as detected by Southern blot analysis, indicating adequate preservation of mRNA. The 6 positive cases were among 4 of 34 adult lymphomas, as compared with 2 of 3 childhood cases. Five of 17 T-lineage cases were t(2;5)-positive, compared with 1 of 15 B-lineage cases and none of the 5 null-cell or mixed lineage cases. Our results therefore show that t(2;5) occurs at a low frequency among CD30+ lymphomas, at least in our adult-dominated series.
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PMID:Low frequency association of the t(2;5)(p23;q35) chromosomal translocation with CD30+ lymphomas from American and Asian patients. A reverse transcriptase-polymerase chain reaction study. 785 44


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