Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:A9QXG9 (bcl-2)
 7,497 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Follicular lymphoma is a low grade malignancy characterized by the translocation t(14;18), which involves the putative oncogene bcl-2. We describe a 73-year-old patient presenting with Burkitt acute lymphoblastic leukemia (B-ALL) L3 (Burkitt type), whose cells had the following immunophenotype: CD19+, CD22+, HLA-DR+, CD10+, TdT-, Cyt IgM-, CD34-. Analysis of 25 peripheral blood metaphases showed the presence of t(14;18) (q32;q21), and t(8;14) (q24;q32) in 24 cells and t(14;18) only in one cell, suggesting that the latter translocation came first during clonal evolution. Both bcl-2 and c-myc were rearranged in addition to the immunoglobulin heavy and light chain genes. The presence of small lymphoid cells in paratrabecular areas on the bone marrow biopsy, together with evidence of cytogenetic clonal evolution, was indicative of a transformation from a low grade follicular lymphoma to a more aggressive Burkitt type malignancy.
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PMID:Translocations t(14;18) and t(8;14) with rearranged bcl-2 and c-myc in a case presenting as B-ALL (L3). 199 60

Centrocytic lymphomas are defined in the Kiel classification as B-cell lymphomas composed exclusively of cells resembling cleaved follicular center cells (FCC). These lymphomas have been shown to be histologically, immunophenotypically, and clinically distinct from other cleaved FCC lymphomas. DNA from 18 centrocytic lymphomas (14 patients) was analyzed using Southern blotting and probes for immunoglobulin heavy (JH) and kappa light chain (JK) joining gene, T-cell receptor beta chain constant gene (CB), bcl-1, bcl-2, and c-myc gene rearrangements. All of the lymphomas had JH and JK rearrangements, confirming their B-cell origin. None of the specimens had detectable CB, bcl-2, or c-myc rearrangements. However, 4 of 14 patients (28.6%) had rearrangement of the chromosome 11 bcl-1 locus. Therefore, centrocytic lymphomas are genotypically distinguishable from the majority of other small cleaved FCC lymphomas by their lack of demonstrable bcl-2 rearrangements. This supports the distinct nature of centrocytic lymphomas and suggests the lack of importance for the putative oncogene bcl-2 in these cases. Furthermore, the frequent rearrangement of bcl-1 suggests a possible role for this locus in the pathogenesis of at least some centrocytic lymphomas.
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PMID:Genotypic characterization of centrocytic lymphoma: frequent rearrangement of the chromosome 11 bcl-1 locus. 220 14

The putative oncogene bcl-2 is juxtaposed to the immunoglobulin heavy chain (Igh) locus by the t(14;18) chromosomal translocation typical of human follicular B-cell lymphomas. The bcl-2 gene product is not altered by the translocation, but its expression is deregulated, presumably by the Igh enhancer E mu. Constitutive bcl-2 expression seems to augment cell survival, as infection with a bcl-2 retrovirus enables certain growth factor-dependent mouse cell lines to maintain viability when deprived of factor. Furthermore, high levels of the bcl-2 product can protect human B and T lymphoblasts under stress and thereby confer a growth advantage. Mice expressing a bcl-2 transgene controlled by the Igh enhancer accumulate small non-cycling B cells which survive unusually well in vitro but do not show a propensity for spontaneous tumorigenesis. In contrast, an analogous myc transgene, designed to mimic the myc-Igh translocation product typical of Burkitt's lymphoma and rodent plasmacytoma, promotes B lymphoid cell proliferation and predisposes mice to malignancy in pre-B and B lymphoid cells. Previous experiments have suggested that bcl-2 can cooperate with deregulated myc to improve in vitro growth of pre-B and B cells. Here we describe a marked synergy between bcl-2 and myc in doubly transgenic mice. E mu-bcl-2/myc mice show hyperproliferation of pre-B and B cells and develop tumours much faster than E mu-myc mice. Suprisingly, the tumours derive from a cell with the hallmarks of a primitive haemopoietic cell, perhaps a lymphoid-committed stem cell.
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PMID:Novel primitive lymphoid tumours induced in transgenic mice by cooperation between myc and bcl-2. 225 Jul 4

cDNA clones of mouse bcl-2 have been isolated and characterized by homology to the human bcl-2 gene, a putative oncogene that is found on the portion of chromosome 18 characteristically involved in the t(14;18) translocation present in nearly all human follicular B cell lymphomas. Our mouse cDNA clone detects 7.9 and 6.3-kb bcl-2 RNAs in mouse B cell lymphomas, but only in tumors consisting of pre-B and follicular center mature B cells, not in pro-B cell or plasma cell tumors. Thus, this gene appears to be a B cell differentiation marker that is expressed only in committed B cells, but is shut off in end stage plasma cells. This pattern of expression is unique among oncogenes, and we suggest that it may be responsible for the high frequency of translocations at this locus in the common malignancy of human mature B cells, follicular lymphomas.
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PMID:Expression of the bcl-2 gene in mouse B lymphocytic cell lines is differentiation stage specific. 310 72

The karyotypic abnormality t(14;18)(q32;q21) is reported to occur in 75% of follicular lymphomas. This translocation results in the rearrangement of a putative oncogene bcl-2, which resides at chromosome 18 band q21 (the 18q21 gene). Using two human genomic DNA fragments cloned from the chromosome 18 band q21 as probes, we analyzed 65 uncultured human lymphoma samples by the Southern blot technique. The 18q21 gene was rearranged in 18 of 26 (69%) follicular lymphomas, 3 of 5 (60%) follicular lymphomas transformed to large cell lymphomas, 8 of 20 (40%) diffuse large cell lymphomas (DLCLs), and 2 of 7 (29%) small noncleaved cell lymphomas (SNCs). Our analysis detected rearrangement of the 18q21 gene in 10 of 13 (77%) cases in which the t(14;18)(q32;q21) translocation was found by cytogenetic techniques. Our analysis also proved helpful in difficult karyotyping situations: (a) identifying the donor chromosome fragment as chromosome 18 band q21 in 4 of 9 (44%) cases that cytogenetically displayed a 14q+ chromosome of unknown origin, and (b) identifying a rearrangement of chromosome 18 band q21 in 12 of 18 (67%) cases that cytogenetically yielded no cells in metaphase. We also demonstrated three cases of submicroscopic rearrangement of the 18q21 gene. In our studies, patients with DLCLs and rearrangement of the 18q21 gene had a significantly higher incidence of extranodal involvement when compared with patients with DLCLs and no 18q21 gene rearrangement (P = 0.03).
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PMID:The gene located at chromosome 18 band q21 is rearranged in uncultured diffuse lymphomas as well as follicular lymphomas. 329 9

We have established a cell line, which we named 380, from a young male with acute lymphoblastic leukemia (FAB type L2). Karyologic analysis of this cell line indicates that it carries an 8;14 and a 14;18 chromosome translocation, which are characteristic of Burkitt lymphoma and of follicular lymphoma, respectively. This cell line is Epstein-Barr virus antigen-negative, reacts with monoclonal antibodies specific for B cells, and contains rearranged immunoglobulin heavy and light chain genes, but does not express human immunoglobulins. In this cell line, both mu heavy chain constant (C mu) loci are rearranged within the joining (JH) DNA segment. One of the JH segments on one of the 14q+ chromosomes is rearranged with a segment of chromosome 8, where the c-myc oncogene resides, while the other is rearranged with a segment of chromosome 18 where a putative oncogene, which we have called bcl-2, is located. The c-myc oncogene, which is translocated to one of the 14q+ chromosomes, is in its germ-line configuration more than 14 kilobases away from both the JH segment and the heavy chain enhancer that is located between the JH and mu switch region. Based on these findings, we propose a model of some aspects of B-cell oncogenesis according to which B-cell neoplasms carrying translocations involving the heavy chain loci on both human chromosomes 14 are the result of a multiple step process.
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PMID:A 14;18 and an 8;14 chromosome translocation in a cell line derived from an acute B-cell leukemia. 633 5

Cloning of the t(14;18) translocation breakpoint resulted in the identification of a new putative oncogene, which mapped to 18q21, termed bcl-2. The t(14;18) resulted in inappropriately high levels of bcl-2 expression in follicular lymphoma. Prospective studies using mice transgenic for a human bcl-2-immunoglobulin minigene, intended to recreate the molecular features of the t(14;18), demonstrated that bcl-2 gene deregulation was oncogenic. Interestingly, overexpression of bcl-2 showed no demonstrable influence on rates of cellular proliferation. Rather, bcl-2 was found to extend cellular viability by blocking apoptosis. Recent studies with other oncogenes and tumor suppressor genes, such as c-myc and p53, have demonstrated that the deregulation of apoptosis may be of general significance in the development of multiple types of cancer and appears to be a critical event during multistep carcinogenesis. The selective induction of apoptosis in tumor cell populations is now being considered in the design of novel therapeutic interventions.
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PMID:The bcl-2 oncogene: apoptosis and neoplasia. 827 71