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Programmed cell death 4 (PDCD4) is a tumor suppressor characterized by its MA3 domain-mediated binding to eIF4A, which suppresses protein synthesis. Its primary functions include inhibiting cell proliferation, invasion, and metastasis, as well as promoting apoptosis. Leukemia is a clonally hematologic malignancy whose pathogenesis is driven primarily by the aberrant activation of key signaling pathways. These dysregulated signals promote enhanced self-renewal, uncontrolled proliferation, impaired differentiation, and blocked apoptosis, collectively arresting leukemic cells at various stages of development. Recent studies have demonstrated a close association between PDCD4 and leukemia development, indicating that PDCD4 regulates this process mainly by participating in abnormally activated signaling pathways. This review examines the expression and regulation of PDCD4 in leukemia, with a focus on its role as a molecular hub that connects the JAK/STAT, PI3K/AKT, and MAPK signaling pathways into a comprehensive network of leukemia pathways. Furthermore, the potential value of PDCD4 in the treatment of leukemia is discussed.