B-cell lymphoma 2-related protein A1 (BCL2A1) (BCL2A1)

B-cell lymphoma 2-related protein A1 (BCL2A1), also known as BFL-1, is a crucial anti-apoptotic member of the BCL-2 family that regulates programmed cell death [1, 3, 6]. It functions by binding and sequestering pro-apoptotic BH3-only proteins, such as BIM and PUMA, thereby preventing mitochondrial outer membrane permeabilization and the subsequent release of cytochrome c [1, 7, 9]. In healthy tissues, BCL2A1 is mainly expressed in the hematopoietic system and is strongly induced by NF-κB signaling in response to inflammatory stimuli [1, 3, 9]. Overexpression of BCL2A1 is a common feature in several cancers, including melanoma, chronic lymphocytic leukemia, and acute myeloid leukemia, where it facilitates tumor progression and serves as a major driver of resistance to chemotherapy and targeted therapies [1, 4, 16]. Specifically, BCL2A1 is a primary factor in acquired resistance to the BCL-2 inhibitor venetoclax in hematologic malignancies [4, 8, 16, 17]. Current therapeutic strategies focus on developing selective BH3 mimetics to neutralize BCL2A1 and restore apoptotic sensitivity in resistant tumors [2, 4, 7].

Other names

BFL1BFL-1GRSHBPA1BCL2L5B-cell leukemia/lymphoma 2-related protein A1Hemopoietic-specific early response proteinProtein GRSBcl-2-related gene expressed in fetal liver

BH3 mimetic antagonism of anti-apoptotic BCL-2 family proteins