Bcl-2 gene promotes haemopoietic cell survival and cooperates with c-myc to immortalize pre-B cells

@article{Vaux1988Bcl2GP,
  title={Bcl-2 gene promotes haemopoietic cell survival and cooperates with c-myc to immortalize pre-B cells},
  author={David L. Vaux and Suzanne Cory and Jerry M. Adams},
  journal={Nature},
  year={1988},
  volume={335},
  pages={440-442}
}
A common feature of follicular lymphoma, the most prevalent haematological malignancy in humans, is a chromosome translocation (t(14;18)) that has coupled the immunoglobulin heavy chain locus to a chromosome 18 gene denoted bcl-2 (refs 1–6). By analogy with the translocated c-myc oncogene in other B-lymphoid tumours (reviewed in ref. 7), bcl-2 is a candidate oncogene, but no biological effects of bcl-2 have yet been reported. To test whether bcl-2 influences the growth of haematopoietic cells… 

Novel primitive lymphoid tumours induced in transgenic mice by cooperation between myc and bcl-2

A marked synergy between bcl-2 and myc in doubly transgenic mice is described, which helps to explain why Eµ–bcl–2/myc mice show hyperproliferation of pre-B and B cells and develop tumours much faster than E²– myc mice.

Oncogenic potential of bcl-2 demonstrated by gene transfer

The bcl-2 gene may represent a novel oncogene having no known retroviral counterpart and its oncogenic potential is demonstrated through a gene transfer approach.

bcl-2 gene expression in hematopoietic cell differentiation

The bcl-2 gene product might have a role in prolonging cell survival and, even in the absence of translocations, might contribute to some of the biologic features that are typical of this disorder.

bcl-2 gene expression in hematopoietic cell differentiation.

The bcl-2 gene product might have a role in prolonging cell survival and, even in the absence of translocations, might contribute to some of the biologic features that are typical of this disorder.

The BCL-2 Gene: A Regulator of Programmed Cell Death

The bcl-2 gene was cloned as a novel gene located at a chromosomal translocation breakpoint in follicular B cell lymphomas, leading to elevated levels of the 26 kd b cl-2 protein and changes in cellular phenotype.

Bcl-2 and c-Myc co-operate in the Epstein – Barr virus-immortalized human B-cell line GM607 but do not confer tumorigenicity

It is shown that the c-Myc and Bcl-2 overexpression, together with EBV immortalization were insufficient to cause full cellular transformation as measured by cell proliferation rates, soft agar and tumorigenicity assays and subtle changes in cellular proliferation and sensitivity to apoptosis were documented.

Expression of the bcl-2 gene in human multiple myeloma cell lines and normal plasma cells.

The bcl-2 gene, encoding a mitochondrial membrane protein suggested to play an important role in cell survival, is translocated into the Ig loci in about 80% of human follicular lymphomas, which

Bcl-2 is an inner mitochondrial membrane protein that blocks programmed cell death

It is demonstrated that Bcl-2 is an integral inner mitochondrial membrane protein of relative molecular mass 25,000 (25k) being localized to mitochondria and interfering with programmed cell death independent of promoting cell division.
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References

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There is a marked deregulation of Bcl-2 when it is introduced into the Ig locus in t(14;18) lymphomas, which has implications for hematopoietic lineages including T cells.

Expression of the c-myc oncogene under control of an immunoglobulin enhancer in E mu-myc transgenic mice

The absence of detectable endogenous c-myc RNA in any tumor, or in preneoplastic bone marrow, supports a negative feedback model for normal c- myc regulation.

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A DNA probe obtained appears to identify bcl-2, a gene locus on chromosome 18 (band q21) that is unrelated to known oncogenes and may be important in the pathogenesis of B-cell neoplasms with this translocation.

Pre-B-cell leukemia with a t(8; 14) and a t(14; 18) translocation is preceded by follicular lymphoma.

The data are consistent with the previous hypothesis on the evolution of B-cell malignancies: a rare pre-B cell develops a t(14; 18) translocation during immunoglobulin VDJ joining that results in an expansion of a follicular lymphoma clone carrying an activated bcl-2 gene.

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Transgenic mice bearing the cellular myc oncogene coupled to the immunoglobulin μ or κ enhancer frequently develop a fatal lymphoma within a few months of birth and constitutive c-myc expression appears to be highly leukaemogenic at several stages of B-cell maturation.