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Venetoclax + mitoxantrone hydrochloride liposome + azacitidine is an investigational triple-drug chemotherapy regimen for adults with acute myeloid leukemia (AML), studied particularly as first-line therapy and in venetoclax/hypomethylating agent–resistant disease. Venetoclax is an oral small-molecule inhibitor of the anti-apoptotic protein B‑cell lymphoma 2 (BCL‑2), promoting mitochondrial pathway–mediated apoptosis in leukemic blasts.[3][15] Azacitidine is a hypomethylating cytidine analog that becomes incorporated into DNA and RNA, inhibits DNA methyltransferases, induces DNA hypomethylation, and directly cytotoxically impairs abnormal hematopoietic cells.[1][3] Mitoxantrone hydrochloride liposome is a liposomal formulation of the anthracenedione mitoxantrone, a topoisomerase II–targeting cytotoxic agent that intercalates into DNA and inhibits DNA replication and repair.[1][3][10] In combination, this regimen is intended to couple BCL‑2–dependent apoptotic priming (venetoclax) with hypomethylating and cytotoxic stress (azacitidine) and intensified DNA-damaging chemotherapy via liposomal mitoxantrone, with the goal of improving remission depth and overcoming resistance to venetoclax plus hypomethylating agents in AML.[1][3][9][10][12]
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