Download Gene Section BCL2 (B-cell leukemia/lymphoma 2) Atlas of Genetics and Cytogenetics

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in Oncology and Haematology
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BCL2 (B-cell leukemia/lymphoma 2)
Jean-Loup Huret
Genetics, Dept Medical Information, University of Poitiers, CHU Poitiers Hospital, F-86021 Poitiers, France
Published in Atlas Database: May 1998
Online updated version: http://AtlasGeneticsOncology.org/Genes/BCL2ID49.html
DOI: 10.4267/2042/37449
This work is licensed under a Creative Commons Attribution-Non-commercial-No Derivative Works 2.0 France Licence.
© 1998 Atlas of Genetics and Cytogenetics in Oncology and Haematology
dimerization, especially with BAX; role of the BCL2
anti-apoptosis members in forming complexes with
caspase-9 and APAF1 (homolog of the nematode CED4), which prevent them to initiate the protease cascade
(through caspase-3 cytochrome C dependent activation
and) leading to apoptosis.
Identity
Location: 18q21
DNA/RNA
Homology
With Ced9 (nematode C. elegans); with other member
of the BCL2 family: 1- apoptosis inhibitors BCLX,
MCL1, and 2- apoptosis inducers BAX, BAD, BIK, …
Implicated in
BCL2 (18q21) PAC 248E24 - Courtesy Mariano Rocchi.
Description
t(14;18)(q32;q21)/B-cell malignancies
→ IgH - BCL2
Telomere to centromere orientation; 3 exons; exon 1
and the 3' part of exon 3 are non coding.
Disease
B-cell NHL mainly; found in 80 to 90% of follicular
lymphomas, 30% of diffuse large cell lymphomas.
Prognosis
According to the cyto-pathologic subtype: small
cleaved cell follicular lymphomas have a good
prognosis; large cell lymphomas have a worse
prognosis; the t(14;18) may have no prognostic
significance.
Cytogenetics
Complex karyotypes are frequent with +7, del(6q),
+12, + X, …
Hybrid/Mutated Gene
5' BCL2 translocated on chromosome 14 near JH
(junctions genes of IgH) and C in 3'.
Abnormal Protein
No fusion protein, but promoter exchange; the
immunoglobulin gene enhancer stimulates the
expression of BCL2.
Transcription
2 alternative transcripts (a and b); 5.1 kb mRNA;
coding sequence: CDS 1459...2178.
Protein
Description
25 kDa; 205 amino acids (BCL2b) or 239 amino acids
(BCL2a, which has, in addition, a hydrophobic tail for
membrane anchorage; this tail seems necessary for anti
apoptotic ability); contain homo/heterodimerization
domains (BH) and NH domains.
Expression
Wide; in B and T cells in particular.
Localisation
Mainly in the
membranes.
mitochondrial
membrane;
other
Function
Antiapoptosis, through a possibly complex process;
Atlas Genet Cytogenet Oncol Haematol. 1998;2(4)
113
BCL2 (B-cell leukemia/lymphoma 2)
Huret JL
Oltvai ZN, Milliman CL, Korsmeyer SJ. Bcl-2 heterodimerizes
in vivo with a conserved homolog, Bax, that accelerates
programmed cell death. Cell 1993 Aug 27;74(4):609-19.
Oncogenesis
As BCL2 is an apoptosis inhibitor, cell death is
delayed, and there is cell accumulation (more than real
transformation).
Taskén K, Skålhegg BS, Taskén KA, Solberg R, Knutsen HK,
Levy FO, Sandberg M, Orstavik S, Larsen T, Johansen AK,
Vang T, Schrader HP, Reinton NT, Torgersen KM, Hansson V,
Jahnsen T. Structure, function, and regulation of human cAMPdependent protein kinases. Adv Second Messenger
Phosphoprotein Res 1997;31:191-204,.
Chronic lymphocytic leukaemia
Oncogenesis
BCL2 is hypomethylated in the promotor region, and,
therefore, overexpressed.
Hu Y, Benedict MA, Wu D, Inohara N, Núñez G. Bcl-XL
interacts with Apaf-1 and inhibits Apaf-1-dependent caspase-9
activation. Proc Natl Acad Sci USA 1998 Apr 14;95(8):438691.
References
Bakhshi A, Jensen JP, Goldman P, Wright JJ, McBride OW,
Epstein AL, Korsmeyer S. Cloning the chromosomal
breakpoint of t(14;18) human lymphomas: clustering around JH
on chromosome 14 and near a transcriptional unit on 18. Cell
1985 Jul;41(3):899-906.
This article should be referenced as such:
Huret JL. BCL2 (B-cell leukemia/lymphoma 2). Atlas Genet
Cytogenet Oncol Haematol.1998;2(4):113-114.
Cleary ML, Sklar J. Nucleotide sequence of a t(14;18)
chromosomal breakpoint in follicular lymphoma and
demonstration of a breakpoint-cluster region near a
transcriptionally active locus on chromosome 18. Proc Natl
Acad Sci USA 1985 Nov;82(21):7439-43.
Atlas Genet Cytogenet Oncol Haematol. 1998;2(4)
114