venetoclax + decitabine + azacitidine + aclarubicin

A combination therapy regimen consisting of venetoclax (a BCL-2 inhibitor), decitabine and azacitidine (hypomethylating agents), and aclarubicin (an anthracycline antitumor drug). Venetoclax is a potent, selective oral BCL-2 inhibitor that works by antagonizing BCL-2, which maintains myeloblast survival by sequestering pro-apoptotic BAX. When BCL-2 is inhibited, BAX is released, causing mitochondrial outer membrane permeabilization and triggering cell death. Decitabine and azacitidine are hypomethylating agents (HMAs) that have demonstrated synergistic effects when combined with venetoclax in preclinical models of AML cells. Azacitidine may reduce levels of MCL-1, an anti-apoptotic protein critical in AML pathogenesis and a possible source of resistance to venetoclax. Aclarubicin is an anthracycline antitumor drug and a type II topoisomerase inhibitor. It prevents topoisomerase II from binding to DNA primarily by intercalating into DNA strands, resulting in chromatin damage without causing direct DNA damage. It also causes epigenetic changes, DNA damage response signals, and apoptosis. Additionally, aclarubicin affects mitochondrial respiratory function in the cytoplasm. This regimen targets multiple pathways involved in leukemia cell survival and proliferation and is primarily used in the treatment of acute myeloid leukemia (AML), particularly in elderly patients or those who cannot tolerate intensive chemotherapy.