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
TLDR
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
TLDR
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
TLDR
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.
TLDR
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
TLDR
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.
Gene Transfer Investigations of Oncogenes Activated by Chromosomal Translocations in Human Lymphomas and Leukemias: BCL2 and C-MYC
TLDR
In a human B-cell line, BCL2 and C-MYC enhanced in vitro growth and tumorigenicity, providing direct evidence for their importance in the pathogenesis of the human B -cell lymphomas and suggesting that they control complementary growth pathways in lymphoid cells.
bcl-2-Immunoglobulin transgenic mice demonstrate extended B cell survival and follicular lymphoproliferation
Human follicular B cell lymphomas possess a t(14;18) interchromosomal translocation that juxtaposes the putative proto-oncogene bcl-2 with the immunoglobulin (Ig) heavy chain locus. We generated
Bcl-2 and c-Myc co-operate in the Epstein – Barr virus-immortalized human B-cell line GM607 but do not confer tumorigenicity
TLDR
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 gene family and the regulation of programmed cell death.
TLDR
The BCL-2 gene was identified at the chromosomal breakpoint of t(14; 18)-bearing human follicular B cell lymphomas and proved to block programmed cell death rather than promote proliferation, initiating a new category of oncogenes, regulators of cell death.
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References

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TLDR
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.
The c-myc oncogene perturbs B lymphocyte development in Eμ-myc transgenic mice
TLDR
It is found that early stages are overrepresented, even before birth, and a normal function of c-myc may be to regulate differentiation as well as to promote cell cycling.
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TLDR
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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TLDR
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.
TLDR
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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TLDR
The data suggest that v-fms encodes a promiscuous tyrosine kinase able to transform cells of the myeloid lineage that do not normally express CSF-1 receptors.
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A retrovirus encoding polyoma middle T antigen has been used to infect a murine hemopoietic cell line (FDC‐P1) dependent on either granulocyte‐macrophage colony‐stimulating factor (GM‐CSF) or
The c-myc oncogene driven by immunoglobulin enhancers induces lymphoid malignancy in transgenic mice
TLDR
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.
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TLDR
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Cloning and structural analysis of cDNAs for bcl-2 and a hybrid bcl-2/immunoglobulin transcript resulting from the t(14;18) translocation
TLDR
The results suggest that t(14;18) translocations alter expression of the bcl-2 gene both by transcriptional activation and by abnormal posttranscriptional regulation of bCl-2 mRNA.
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