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Bcl-2 is a pro-survival oncogene that promotes leukemogenesis by blocking programmed cell death. Therefore, agents designed to disrupt the anti-apoptotic signaling pathway are considered for the treatment of hematological malignancies, including Bcl-2 inhibitors like venetoclax. Another subfamily of ‘BH3-only’ proteins induce apoptosis by binding to BCL-2. Agonists for pro-apoptotic proteins, like ‘BH3-only’ proteins, are in development.