Targeting cell death pathways in acute myeloid leukemia: Molecular mechanisms and clinical implications (Review)

Acute myeloid leukemia (AML) is a highly heterogeneous hematologic malignancy, characterized by complex molecular features and mechanisms of treatment resistance, which lead to a poor prognosis and high relapse rates. The complexity of multi‑pathway interactions and the dysregulated dynamics of tumor cell death pathways may contribute to the wide range of clinical outcomes observed despite advancements in current therapies. Most current research focuses on a single form of cell death, neglecting the mechanisms of other death pathways and their synergistic interactions, which hinders the development of novel therapeutic approaches. The present review systematically integrates and compares the molecular features of key cell death modalities in AML, including autophagy, apoptosis, pyroptosis, necroptosis, ferroptosis and cuproptosis. The present review analyzes their specific triggers, signaling hubs and regulatory networks within the metabolic microenvironment, and discusses the dynamic crosstalk among these pathways. A key focus is the therapeutic potential of exploiting this crosstalk to design synergistic combination therapies. To overcome the limitations of conventional treatments and improve patient outcomes, it is essential to further investigate the transition mechanisms of various cell death modes in AML progression, drug resistance and relapse. Additionally, establishing a theoretical foundation for the development of innovative therapies that synergistically regulate multiple death pathways is crucial.