BCL2

BCL2 Background

BCL2 is a proto-oncogene that was discovered at the chromosomal breakpoint of t(14;18) bearing human B-cell lymphomas ^[1]. The BCL2 gene encodes Bcl-2 (B-cell lymphoma 2), a multiple-domain anti-apoptotic protein. Pablo Mozas et al. found that in chronic lymphocytic leukemia (CLL) cells, excess of BCL2 and other anti-apoptotic proteins sequesters pro-apoptotic molecules such as BIM and BID, thus blocking the activation of BAK or BAX and subsequent apoptosis ^[2]. Many cancer cells, including most B cell-derived lymphomas, colorectal adenocarcinomas, and undifferentiated nasopharyngeal cancers have been detected Bcl-2 overexpression ^[3]. The unique oncogenic role of Bcl-2 has largely assumed its extending cell survival by inhibiting a variety of apoptotic deaths. Bcl-2 has been also involved in the resistance of many cancers to treatment with radiation and chemotherapeutic agents ^[4][5]. The functional ablation of Bcl-2 or other antiapoptotic proteins, such as Bcl-xL, could either induce apoptosis in cancer cells or sensitize these cells for chemotherapy. Therefore, Bcl-2 represents a target for the treatment of cancers, especially those in which Bcl-2 is overexpressed and for which traditional therapy has failed ^[3][6]. Mutations in the hydrophobic groove region within Bcl-2 protein have been shown to abolish its antiapoptotic activity and disrupt heterodimerization with other family members ^[6]. Yin X M et al. also proved that BH1 and BH2 domains of Bcl-2 are indispensable for apoptotic repression and heterodimerization With Bax ^[7].

[1] Tsujimoto Y, Finger LR, et al. Cloning of the chromosome breakpoint of neoplastic B cells with the t(14;18) chromosome translocation [J]. Science. 1984 Nov 30; 226(4678):1097-9.
[2] Valentín Ortíz-Maldonado, Pablo Mozas, et al. The biology behind B-cell lymphoma 2 as a target in chronic lymphocytic leukemia [J]. Ther Adv Hematol. 2016 Dec; 7(6): 321-329.
[3] Berghella A M, Pellegrini P, et al. Bcl-2 and Drugs Used in the Treatment of Cancer: New Strategies of Biotherapy Which Should Not Be Underestimated [J]. Cancer Biother Radiopharm, 1998, 13:225-236.
[4] Reed J C. Mechanisms of Apoptosis Avoidance in Cancer [J]. Curr Opin Oncol,1999, 11:68-75.
[5] Kusenda J Bcl-2 family proteins and leukemia [J]. Neoplasma (Bratisl), 1998, 45:117-122.
[6] Nicholson D W From Bench to Clinic With Apoptosis-Based Therapeutic Agents [J]. Nature (London) 2000, 407:810-816.
[7] Yin X M, Oltvai Z N, et al. BH1 and BH2 Domains of Bcl-2 Are Required for Inhibition of Apoptosis and Heterodimerization With Bax [J]. Nature (London) 1994, 369:321-323.