B-Cell Leukemia/Lymphoma 2 (BCL-2) is a key protein regulator of apoptosis, which is the process of programmed cell death. The BCL-2 protein is encoded by the BCL2 gene in humans and is the founding member of the BCL-2 family of regulator proteins. This family includes both pro-apoptotic and anti-apoptotic proteins that play crucial roles in the regulation of cell death and survival .
The BCL-2 gene was first identified in chromosomal translocations involving chromosomes 14 and 18 in follicular lymphomas. This translocation results in the overexpression of the BCL-2 protein, which inhibits apoptosis and allows cells to survive longer than they should, contributing to the development of cancer .
BCL-2 is localized to the outer membrane of mitochondria, where it promotes cellular survival by inhibiting the actions of pro-apoptotic proteins such as Bax and Bak. These pro-apoptotic proteins normally act on the mitochondrial membrane to promote permeabilization and release of cytochrome c and reactive oxygen species (ROS), which are important signals in the apoptosis cascade .
Damage to the BCL-2 gene has been identified as a cause of several cancers, including melanoma, breast cancer, prostate cancer, chronic lymphocytic leukemia, and lung cancer. Overexpression of BCL-2 alone does not cause cancer, but when combined with the overexpression of the proto-oncogene myc, it can lead to aggressive B-cell malignancies, including lymphoma .
The development of BCL-2 inhibitors has been a significant advancement in cancer therapy. Venetoclax is the first selective BCL-2 inhibitor and has been approved for the treatment of chronic lymphocytic leukemia (CLL) and acute myeloid leukemia (AML). Venetoclax works by inhibiting BCL-2, thereby triggering apoptosis in cancer cells .
The mouse anti-human BCL-2 antibody is derived from the hybridization of mouse FO myeloma cells with spleen cells from BALB/c mice immunized with recombinant human BCL-2 amino acids 1-211 purified from E. coli . This antibody is used in research to study the expression and function of BCL-2 in various human tissues and cells.