Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0023418 (leukemia)
 93,477 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Gel filtration chromatography of disrupted bovine leukaemia virus (BLV) resulted in the isolation of the 25000 mol. wt. major internal protein (p25), two previously uncharacterized proteins of mol. wt 65000 (p65) and 12000 (p12), and a mixture of p12 and a protein of mol. wt. 15000 (p15). The p65 protein does not bind to concanavalin A and its antigenicity is ether resistant. Therefore, this polypeptide is different from the previously described glycoprotein associated with BLV. Radioimmunoprecipitation and competitive radioimmunoassays indicated that the p65 protein shares antigenic determinants with the p25, p15 and p12 proteins, respectively. Furthermore, tryptic peptide mapping demonstrated that p65 contains p25, p15, p12 and a BLV protein of mol. wt. 10000 (p10). These results are consistent with the view that p65 is the precursor of gag gene-derived core proteins of BLV.
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PMID:Detection of a precursor-like protein of bovine leukaemia virus structural polypeptides in purified virions. 615 29

A retrovirus belonging to the family of recently discovered human T-cell leukemia viruses (HTLV), but clearly distinct from each previous isolate, has been isolated from a Caucasian patient with signs and symptoms that often precede the acquired immune deficiency syndrome (AIDS). This virus is a typical type-C RNA tumor virus, buds from the cell membrane, prefers magnesium for reverse transcriptase activity, and has an internal antigen (p25) similar to HTLV p24. Antibodies from serum of this patient react with proteins from viruses of the HTLV-I subgroup, but type-specific antisera to HTLV-I do not precipitate proteins of the new isolate. The virus from this patient has been transmitted into cord blood lymphocytes, and the virus produced by these cells is similar to the original isolate. From these studies it is concluded that this virus as well as the previous HTLV isolates belong to a general family of T-lymphotropic retroviruses that are horizontally transmitted in humans and may be involved in several pathological syndromes, including AIDS.
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PMID:Isolation of a T-lymphotropic retrovirus from a patient at risk for acquired immune deficiency syndrome (AIDS). 618 83

A glycoprotein of molecular weight 130,000 (gP130) has been precipitated from the cytoplasm of GR-strain mouse mammary tumor (GR-MMT) cells by a rabbit antiserum (anti-MMTV) to GR-strain mouse mammary tumor virus (GR-MMTV). This protein was not precipitated by antisera specific for detergent-disrupted C3H-strain MMTV (C3H-MMTV); C3H-MMTV glycoproteins; C3H-MMTV nonglycosylated proteins; GR-MMTV p25 or p12; RIII strain (milk) MMTV proteins; or Rauscher murine leukemia virus (R-MuLV) proteins; nor was it precipitated by normal rabbit serum. Two-dimensional thin layer analysis of 35S-methionine-containing tryptic peptides revealed that five of nine gp33 peptides and one of seven gp55 peptides are shared by gP130 and gPr76env. The envelope protein precursor, gPr76env, contains all of the gp33 peptides and six of seven gp55 peptides. One peptide in gPr76env, possibly a gp55-gp33 junction peptide, is also apparently present in gP130. Six of ten p25 peptides and four more gag-related peptides are shared by PR78gag and gP130. Protein gP130 also contains several tryptic peptides not found in gPr76env or in the core protein precursors Pr78gag, Pr110gag or Pr180gag-pol. Radioimmunoprecipitation experiments showed that gP130 could be precipitated from extracts of GR-MMTV cells with anti-MMTV serum even after antibodies to the known MMTV structural proteins had been removed from the serum by absorption. Both gP130 and a second protein, p30, were found in immunoprecipitates of detergent-disrupted isotopically labeled GR-MMTV treated with the absorbed anti-MMTV serum. These results suggest that antibodies to gP130 in the anti-MMTV serum are capable of recognizing those protein sequences unique to gP130; that is, those protein sequences which are not related to viral structural proteins. In light of these data and data published previously, gP130 is apparently a polyprotein containing juxtaposed components translated from the 5' and 3' end of the MMTV genome and protein components not previously identified as virus-specific.
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PMID:A unique glycoprotein containing GR-mouse mammary tumor virus peptides and additional peptides unrelated to viral structural proteins. 625 70

The major internal protein of bovine leukemia virus (BLV p24) was isolated using ion exchange chromatography on phosphocellulose and gel filtration. The specificity of the BLV p24 isolated was checked by both the radioimmunoprecipitation (RIP) and the competitive radioimmunoassay (RIA). No cross reactivity between BLV p25 and the mammalian viruses of type C and D and the retrovirus isolated from human myeloma cells RPMI8226 [8, 17] was detected. The analysis of 429 leukemia-suspected bovine blood sera resulted in the detection of 165 (38.5%) positive and 264 (61.5%) negative blood sera. A correlation of the results of radioimmunoprecipitation reaction of major internal protein p24 and immunodiffusion test on the glycoprotein antigen of BLV was observed.
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PMID:Radioimmunoassay for major internal structural protein (p21) of the bovine leukemia virus; antibodies detection and viruses identification. 626 68

MUM1 (multiple myeloma oncogene 1)/IRF4 (interferon regulatory factor 4) gene has been identified as an oncogene transcriptionally activated by t(6;14)(p25;q32) chromosomal translocation in multiple myeloma (MM). The significance of this alteration in MM remains unknown, as it is not detectable by means of conventional cytogenetic analysis. To address this issue, we established diagnostic procedures based on pulsed-field gel electrophoresis (PFGE) analysis and double color fluorescence in situ hybridization (DCFISH) using DNA probes derived from the MUM1 and the immunoglobulin heavy chain (IgH) gene loci. Among a panel of 17 MM cell lines, three (17.6%) showed fusions between these two loci, which resulted in the juxtaposition of the MUM1 to the IgH 3' alpha-enhancer region by virtue of t(6;14) or insertion of the IgH sequences into the vicinity of the MUM1 gene and in the concomitant overexpression of the MUM1 mRNA. With similar results, fusions between MUM1 and IgH loci were observed by means of interphase DCFISH in eight (21.1%) out of the 38 MM cases, although no definite relationships between MUM1 status and specific clinical findings could be established.
Leukemia 1999 Nov
PMID:Detection of MUM1/IRF4-IgH fusion in multiple myeloma. 1055 56

MUM1/IRF4 is a myeloma-associated oncogene transcriptionally activated as a result of t(6;14)(p25,q32) chromosomal translocation and by virtue of its juxtaposition to the immunoglobulin heavy chain gene (IgH) locus. When this oncogene becomes non-functional, no activated B/T lymphocytes and Ig secreting plasma cells are observed, suggesting that MUM1/IRF4 is crucial for lymphoid development. Its expression was analyzed in both reactive lymphoid and lymphoma tissues by means of an immunohistochemical technique using specific goat antiserum against MUM1/IRF4. This analysis detected a 50 kDa MUM1 product whose localization was restricted to the nuclei of the lymphocytes. The MUM1+ cells in reactive lymph nodes were found to consist of plasma cells and a small fraction (approximately 7.9%) of B cells harboring CD20+CD38+, which were located in the light zone of the germinal center. MUM1 expression in peripheral blood B/T lymphocytes was upregulated by mitogenic stimuli, suggesting that MUM1 positivity represents the activated state of the B/T cells. In B cell non-Hodgkin's lymphoma (NHL), MUM1 expression was observed in 73.2% (30/41) of diffuse large B cell lymphoma (DLBCL), 20% (1/5) of marginal zone lymphoma (MZL) and 43% (3/7) of small lymphocytic lymphoma (SLL) cases, whereas it was not seen in any cases of mantle cell lymphoma (MCL) or follicle center lymphoma (FCL). Also, MUM1 was stained at high intensity in various types of T cell lymphomas including adult T cell leukemia/lymphoma (ATL/L) and anaplastic large cell lymphoma (ALCL) and in the majority of Hodgkin's diseases. Our results suggest that a major proportion of lymphomas comprise either physiologically or aberrantly activated neoplastic lymphocytes expressing the MUM1 protein.
Leukemia 2000 Mar
PMID:MUM1/IRF4 expression as a frequent event in mature lymphoid malignancies. 1072 Jan 41

We describe a 54-year-old man with CD2, CD7, and CD56-positive but CD3, CD4, and CD8-negative aggressive NK cell lymphoma/leukemia. Chromosome analysis of the peripheral blood cells showed clonal aberration consisting of 46,XY,dup(3)(p21p25),der(3)t(1;3)(q12;p25),del(5)(q13q22), del(6)(q13),del(13)(q12q14). The peripheral blood lymphoma cells contained clonal EBV-DNA by Southern blot analysis. The disease was refractory to chemotherapy and the clinical course was aggressive and rapid. Deletion 6q and deletion 13q have been frequently reported in NK cell lymphoma/leukemia. Thus, some tumor suppressor genes involving NK cell malignancies may be present in these regions.
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PMID:Aggressive NK cell lymphoma/leukemia with clonal der(3)t(1;3) (q12;p25), del(6)(q13) and del(13)(q12q14). 1167 36

Comparative genomic hybridization (CGH) studies have demonstrated a high incidence of chromosomal imbalances in non-Hodgkin's lymphoma. However, the information on the genomic imbalances in Burkitt's Lymphoma (BL) is scanty. Conventional cytogenetics was performed in 34 cases, and long-distance PCR for t(8;14) was performed in 18 cases. A total of 170 changes were present with a median of four changes per case (range 1-22). Gains of chromosomal material (143) were more frequent than amplifications (5) or losses (22). The most frequent aberrations were gains on chromosomes 12q (26%), Xq (22%), 22q (20%), 20q (17%) and 9q (15%). Losses predominantly involved chromosomes 13q (17%) and 4q (9%). High-level amplifications were present in the regions 1q23-31 (three cases), 6p12-p25 and 8p22-p23. Upon comparing BL vs Burkitt's cell leukemia (BCL), the latter had more changes (mean 4.3 +/- 2.2) than BL (mean 2.7 +/- 3.2). In addition, BCL cases showed more frequently gains on 8q, 9q, 14q, 20q, and 20q, 9q, 8q and 14q, as well as losses on 13q and 4q. Concerning outcome, the presence of abnormalities on 1q (ascertained either by cytogenetics or by CGH), and imbalances on 7q (P=0.01) were associated with a short survival.
Leukemia 2003 Oct
PMID:Abnormalities on 1q and 7q are associated with poor outcome in sporadic Burkitt's lymphoma. A cytogenetic and comparative genomic hybridization study. 1451 52

In the course of structure-activity relationship studies, new rebeccamycin derivatives substituted in 3,9-positions on the indolocarbazole framework, and a 2',3'-anhydro derivative were prepared by semi-synthesis from rebeccamycin. The antiproliferative activities against nine tumor cell lines were determined and the effect on the cell cycle of murine leukemia L1210 cells was examined. Their DNA binding properties and inhibitory properties toward topoisomerase I and three kinases PKCzeta, CDK1/cyclin B, CDK5/p25 and a phosphatase cdc25A were evaluated. The 3,9-dihydroxy derivative is the most efficient compound of this series toward CDK1/cyclin B and CDK5/p25. It is also characterized as a DNA binding topoisomerase I poison. Its broad spectrum of molecular activities likely accounts for its cytotoxic potential. This compound which displays a tumor cell line-selectivity may represent a new lead for subsequent drug design in this series of glycosylated indolocarbazoles.
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PMID:Semi-synthesis, topoisomerase I and kinases inhibitory properties, and antiproliferative activities of new rebeccamycin derivatives. 1460 48

Although reciprocal chromosomal translocations are not typical for B-cell chronic lymphocytic leukemia (B-CLL), we identified the novel t(1;6)(p35.3;p25.2) in eight patients with this disorder. Interestingly, all cases showed lack of somatically mutated IgV(H). Clinical, morphological, immunologic, and genetic features of these patients are described. Briefly, the age ranged from 33 to 81 years (median: 62.5 years) and the sex ratio was 6M:2F. Most of the patients (6/8) presented with advanced clinical stage. Therapy was required in seven cases. After a median follow-up of 28 months, five patients are alive and three died from disease evolution. Three cases developed transformation into diffuse large B-cell lymphoma. Translocation t(1;6) was found as the primary karyotypic abnormality in three patients. Additional chromosomal aberrations included changes frequently found in unmutated B-CLL, that is, del(11)(q), trisomy 12 and 17p aberrations. Fluorescence in situ hybridization analysis performed in seven cases allowed us to map the t(1;6) breakpoints to the 1p35.3 and 6p25.2 chromosomal bands, respectively. The latter breakpoint was located in the genomic region coding for MUM1/IRF4, one of the key regulators of lymphocyte development and proliferation, suggesting involvement of this gene in the t(1;6). Molecular characterization of the t(1;6)(p35.3;p25.2), exclusively found in unmutated subtype of B-CLL, is in progress.
Leukemia 2005 Jan
PMID:Translocation t(1;6)(p35.3;p25.2): a new recurrent aberration in "unmutated" B-CLL. 1551 Feb 10


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