B-cell lymphoma 2 apoptosis regulator (Bcl-2)

B-cell lymphoma 2 apoptosis regulator (Bcl-2) is the founding member of the Bcl-2 protein family, critically regulating apoptosis by inhibiting programmed cell death through its action on the mitochondrial membrane. Bcl-2 is encoded by the BCL2 gene and prevents the release of cytochrome c, thus preserving mitochondrial integrity and promoting cell survival. Dysregulation and overexpression of Bcl-2 are oncogenic, underlying several hematological and solid tumors, particularly by blocking apoptosis rather than directly stimulating cell proliferation. Bcl-2 is a prime therapeutic target, with drugs (notably venetoclax) designed to antagonize its apoptotic block, showing transformative effects in hematologic malignancies. Chromosomal translocation *t(14;18)* is a key driver of Bcl-2 overexpression in B-cell lymphomas. Bcl-2 also engages in mitochondrial dynamics and metabolic regulation, and its perturbation is linked to cancer, resistance to therapy, and other diseases. Safety concerns exist, notably thrombocytopenia with less selective inhibitors.

Other names

BCL2B-cell CLL/lymphoma 2BCL2, apoptosis regulatorB cell leukemia/lymphoma 2Bcl-2 apoptosis regulator

BH3-mimetics: adversarial inhibition of BCL2’s anti-apoptotic activity, restoring apoptosis in malignant cells. Direct binding to hydrophobic groove of BCL2 protein, antagonizing BCL2 interactions. Inhibition of BCL2 results in mitochondrial outer membrane permeabilization (MOMP). Activation of caspase cascade via release of cytochrome c from mitochondria.