Alternative titles; symbols
HGNC Approved Gene Symbol: BCL2A1
Cytogenetic location: 15q25.1 Genomic coordinates (GRCh38): 15:79,960,892-79,971,196 (from NCBI)
Programmed cell death (apoptosis) plays an important role in embryonic development, deletion of autoreactive T lymphocytes, and homeostasis. Genes regulating apoptosis include p53 (191170), a tumor suppressor gene, MYC (190080), a protooncogene, and BCL2 (151430). Lin et al. (1993) isolated a novel mouse cDNA sequence, designated BCL2-related protein A1 (Bcl2a1) by them, and identified it as a member of the BCL2 family of apoptosis regulators by the predicted protein sequence. Lin et al. (1996) demonstrated that the A1 protein, although regulated differently from BCL2, has similar antiapoptotic activity. The BCL2A1 gene has also been referred to as BCL2L5, BFL1, and GRS.
Choi et al. (1995) isolated a BCL2-related gene from human fetal liver. Homology to the BH1 and BH2 domains of BCL2 was striking. BFL1 is abundantly expressed in bone marrow and at a low level in some other tissues. A correlation was noted between the expression level of BFL1 and the development of stomach cancer in 8 sets of clinical samples. Choi et al. (1995) speculated that BFL1 is involved in the promotion of cell survival during development or progression of stomach cancer. Choi et al. (1997) showed that BFL1 is the human homolog of murine A1.
D'Sa-Eipper et al. (1996) showed that the BFL1 protein suppresses apoptosis induced by the p53 tumor suppressor protein in a manner similar to other BCL2 family members. The BFL1 gene showed a dominant cooperating oncogenic activity with the E1A oncogene in transformation of primary rodent epithelial cells.
By expression profiling of ALK (105590)-positive anaplastic large cell lymphomas (ALCLs), Piva et al. (2006) identified a large group of ALK-regulated genes. Functional RNA interference screening on a set of these transcriptional targets revealed that CEBPB (189965) and BCL2A1 were absolutely necessary to induce cell transformation and/or to sustain growth and survival of ALK-positive ALCL cells.
Lin et al. (1997) sequenced a portion of the A1 gene, and using the A1 probe on mouse and human DNA panels, demonstrated that the mouse gene is situated on chromosome 9 and the human homolog is on chromosome 15. By fluorescence in situ hybridization analysis, Choi et al. (1997) mapped the human BCL2A1 gene to 15q24.3.
Akatsuka et al. (2003) identified 3 SNPs in the BCL2A1 gene, 2 of which encode minor histocompatibility antigens expressing epitopes for HLA-A*2402- and HLA-B*4403-restricted T-cell clones. They proposed that these minor histocompatibility antigens could be immunotherapeutic targets in cases of recurrent malignancies after allogeneic hemopoietic cell transplantation.
Using mast cells from wildtype and Bcl2a1-deficient mice, Xiang et al. (2001) showed that knockout mice had normal numbers of mast cells in skin, lung, and spleen. Bone marrow-derived mast cells from normal mice expressed Bcl2a1 after activation and, like Bcl2a1-deficient mice, released granule mediators. However, mast cells from Bcl2a1-deficient mice did not survive allergen activation in vitro, and mast cell number was reduced in vivo after allergen sensitization and provocation. Xiang et al. (2001) proposed that BCL2A1 could be a target in the treatment of allergic diseases.
He et al. (2005) studied hyperoxic acute lung injury in wildtype and Bcl2a1-null mice. In wildtype mice exposed to 100% oxygen, TUNEL-positive cell death was accompanied by induction of Bcl2a1, Bcl2, and Bclxl (see 600039) as an apparent protective response, whereas in Bcl2a1-null mice the toxic effects of hyperoxia were exaggerated, Bcl2 and Bclxl were not induced, and premature death was seen. Overexpression of IL11 (147681) in Bcl2a1-null mice revealed significantly reduced IL11-induced protection, survival advantage, and Bcl2 and Bclxl induction compared to wildtype mice. Overexpression of VEGF (192240) conferred protection via a Bcl2a1-dependent mechanism. In vitro hyperoxia also stimulated Bcl2a1, and Bcl2a1 overexpression inhibited oxidant-induced epithelial cell apoptosis and necrosis. He et al. (2005) concluded that BCL2A1 is an important regulator of oxidant-induced lung injury, apoptosis, necrosis, and BCL2 and BCLXL gene expression and a critical mediator of IL11 and VEGF-induced cytoprotection.
Akatsuka, Y., Nishida, T., Kondo, E., Miyazaki, M., Taji, H., Iida, H., Tsujimura, K., Yazaki, M., Naoe, T., Morishima, Y., Kodera, Y., Kuzushima, K., Takahashi, T. Identification of a polymorphic gene, BCL2A1, encoding two novel hematopoietic lineage-specific minor histocompatibility antigens. J. Exp. Med. 197: 1489-1500, 2003. [PubMed: 12771180] [Full Text: https://doi.org/10.1084/jem.20021925]
Choi, S. S., Park, I.-C., Yun, J. W., Sung, Y. C., Hong, S.-I., Shin, H.-S. A novel Bcl-2 related gene, Bfl-1, is overexpressed in stomach cancer and preferentially expressed in bone marrow. Oncogene 11: 1693-1698, 1995. [PubMed: 7478596]
Choi, S. S., Park, S. H., Kim, U.-J., Shin, H.-S. Bfl-1, a Bcl-2-related gene, is the human homolog of the murine A1, and maps to chromosome 15q24.3. Mammalian Genome 8: 781-782, 1997. [PubMed: 9321477] [Full Text: https://doi.org/10.1007/s003359900567]
D'Sa-Eipper, C., Subramanian, T., Chinnadurai, G. Bfl-1, a bcl-2 homologue, suppresses p53-induced apoptosis and exhibits potent cooperative transforming activity. Cancer Res. 56: 3879-3882, 1996. [PubMed: 8752150]
He, C. H., Waxman, A. B., Lee, C. G., Link, H., Rabach, M. E., Ma, B., Chen, Q., Zhu, Z., Zhong, M., Nakayama, K., Nakayama, K. I., Homer, R., Elias, J. A. Bcl-2-related protein A1 is an endogenous and cytokine-stimulated mediator of cytoprotection in hyperoxic acute lung injury. J. Clin. Invest. 115: 1039-1048, 2005. [PubMed: 15841185] [Full Text: https://doi.org/10.1172/JCI23004]
Lin, E. Y., Kozak, C. A., Orlofsky, A., Prystowsky, M. B. The bcl-2 family member, Bcl2al, maps to mouse chromosome 9 and human chromosome 15. Mammalian Genome 8: 293-294, 1997. [PubMed: 9096119] [Full Text: https://doi.org/10.1007/s003359900418]
Lin, E. Y., Orlofsky, A., Berger, M. S., Prystowsky, M. B. Characterization of A1, a novel hemopoietic-specific early-response gene with sequence similarity to bcl-2. J. Immun. 151: 1979-1988, 1993. [PubMed: 8345191]
Lin, E. Y., Orlofsky, A., Wang, H.-G., Reed, J. C., Prystowsky, M. B. A1, a Bcl-2 family member, prolongs cell survival and permits myeloid differentiation. Blood 87: 983-992, 1996. [PubMed: 8562970]
Piva, R., Pellegrino, E., Mattioli, M., Agnelli, L., Lombardi, L., Boccalatte, F., Costa, G., Ruggeri, B. A., Cheng, M., Chiarle, R., Palestro, G., Neri, A., Inghirami, G. Functional validation of the anaplastic lymphoma kinase signature identifies CEBPB and BCL2A1 as critical target genes. J. Clin. Invest. 116: 3171-3182, 2006. [PubMed: 17111047] [Full Text: https://doi.org/10.1172/JCI29401]
Xiang, Z., Ahmed, A. A., Moller, C., Nakayama, K., Hatakeyama, S., Nilsson, G. Essential role of the prosurvival bcl-2 homologue A1 in mast cell survival after allergic activation. J. Exp. Med. 194: 1561-1569, 2001. [PubMed: 11733571] [Full Text: https://doi.org/10.1084/jem.194.11.1561]