The Regimen of Cladribine, Cytarabine, and Venetoclax (CAV) Induces Apoptosis in Acute Myeloid Leukemia Cells by Enhancing DNA Damage

Patients with primary refractory or relapsed acute myeloid leukemia (AML) typically face a poor prognosis. Current chemotherapy regimens do not always achieve complete remission (CR) before transplantation, while facing the dilemma of high organ toxicity and no chance of transplantation in some patients. A combination of cladribine, cytarabine, and venetoclax (CAV) represents a novel salvage regimen. In this study, cladribine, cytarabine, and venetoclax alone or in combination significantly inhibited the proliferation of leukemia cell lines and primary cells in a dose-dependent manner, with the triple CAV combination exerting a far stronger inhibitory effect than any single agent or dual-drug combination (p < 0.01) and showing synergistic interactions (combination index <1). Mechanistically, CAV exerts potent anti-AML effects by synergistically exacerbating DNA damage, inducing apoptosis, arresting the cell cycle at the G0/G1 phase, and promoting differentiation of AML cells toward myeloid/monocyte-macrophage lineages. Collectively, these findings confirm the efficacy of CAV and delineate its multifaceted mechanism of action, thereby providing a well-supported, mechanism-driven combinatorial therapeutic strategy for the management of AML.