Antiapoptotic protein that inhibits anticancer drug-induced apoptosis.
- Bcl-2 (B-cell lymphoma 2), encoded in humans by the BCL2 gene, is the founding member of the Bcl-2 family of regulator proteins that regulate cell death by either inhibiting or inducing apoptosis.
A family of proteins that help regulate intrinsic apoptosis and the overexpression is seen in a variety of solid tumors and felt to play a role in tumor cell survival and resistance to chemotherapy.
Bcl-2 derives its name from B-cell lymphoma 2, as it is the second member of a range of proteins initially described in chromosomal translocations involving chromosomes 14 and 18 in follicular lymphomas.
Like BCL3, BCL5, BCL6, BCL7A, BCL9, and BCL10, it has clinical significance in lymphoma.
There are two isoforms of Bcl-2, Isoform 1, and Isoform 2.
BCL-2 is localized to the outer membrane of mitochondria.
BCL-2 plays an important role in promoting cellular survival and inhibiting the actions of pro-apoptotic proteins.
The pro-apoptotic proteins in the BCL-2 family, including Bax and Bak.
The pro-apoptotic proteins normally act on the mitochondrial membrane to promote the permeability and release of cytochrome C and reactive oxygen species, that are important signals in the apoptosis cascade.
Pro-apoptotic proteins are activated by BH3-only proteins, and are inhibited by the function of BCL-2 and its relative BCL-Xl.
BCL-2 regulates mitochondrial dynamics, and is involved in the regulation of mitochondrial fusion and fission.
Frequently overexpressed in small cell lung cancer, and its up regulation has been seen with chemotherapy resistance.
In pancreatic beta-cells, BCL-2 and BCL-Xl are known to be involved in controlling metabolic activity and insulin secretion: suggesting it has a protective metabolic effect in conditions of high demand.
Damage to the Bcl-2 gene has been identified as a cause of a number of cancers, including melanoma, breast, prostate, chronic lymphocytic leukemia, and lung cancer, and is a possible cause of schizophrenia and autoimmunity.
BCL2 (B-cell lymphoma 2), an antiapoptotic molecule strongly expressed in CLL cells, has emerged as another important therapeutic target.
Overexpression associated with drug resistance in various malignancies.
Plays a key role in determining responsiveness to chemotherapy in tumor cells.
In pancreatic beta-cells, BCL-2 and BCL-Xl are known to be involved in controlling metabolic activity and insulin secretion: suggesting it has a protective metabolic effect in conditions of high demand.
Damage to the Bcl-2 gene has been identified as a cause of a number of cancers, including melanoma, breast, prostate, chronic lymphocytic leukemia, and lung cancer, and is a possible cause of schizophrenia and autoimmunity.
Protein overexpression in leukemia, lymphoma, myeloma, lung cancer, melanoma, breast cancer, colorectal cancer and gastric carcinoma.
May be positive in follicular and mantle zone lymphoma.
Confers resistance to chemotherapy in non-Hodgkin’s chemotherapy treatment.
But simultaneous over-expression of Bcl-2 and the proto-oncogene myc may produce aggressive B-cell malignancies including lymphoma.
A chromosomal translocation commonly occurs between the fourteenth and the eighteenth chromosomes – t(14;18) – which places the Bcl-2 gene from chromosome 18 next to the immunoglobulin heavy chain locus on chromosome 14 in follicular lymphoma.
This fusion gene is deregulated, leading to the transcription of excessively high levels of Bcl-2 , decreasing the propensity of these cells for apoptosis.
Bcl-2 expression is frequent in small cell lung cancer, accounting for 76% cases in one study.
Apoptosis plays an active role in regulating the immune system.
The immune system can cause immune unresponsiveness to self-antigens via both central and peripheral tolerance.
With defective apoptosis, it may contribute to autoimmune diseases.
The autoimmune disease type 1 diabetes can be caused by defective apoptosis, which leads to aberrant T cell Nd defective peripheral tolerance.
Dendritic cells are the immune system’s most important antigen-presenting cells, their activity must be tightly regulated by mechanisms such as apoptosis.
Dendritic cell lifespan may be partly controlled by a timer dependent on anti-apoptotic Bcl-2.
Apoptosis plays an important role in regulating a variety of diseases.
Schizophrenia is a psychiatric disorder in which an abnormal ratio of pro- and anti-apoptotic factors may contribute towards pathogenesis.
Antibodies to Bcl-2 can be used with immunohistochemistry to identify cells containing the antigen.
In healthy tissue, these antibodies react with B-cells in the mantle zone, as well as some, T-cells.
Positive cells increase considerably in follicular lymphoma, as well as many other forms of cancer.
The presence or absence of Bcl-2 staining may be significant for the patient’s prognosis or likelihood of relapse.
Targeted and selective Bcl-2 inhibitors are currently in use.
Oblimersen is an antisense
oligonucleotide drug, that targets Bcl-2.
An antisense DNA or RNA strand is non-coding and complementary to the coding strand, which is the template for producing respectively RNA or protein.
An antisense drug is a short sequence of RNA.
An antisense drug hybridizes with and inactivates mRNA, preventing the protein from being formed.
The highly selective inhibitor venetoclax which inhibits Bcl-2, is approved for anyone with CLL or small lymphocytic lymphoma, with or without 17p deletion, still as a second-line treatment.