Platelet biology in cancer and leukemia: Mechanisms and therapeutic insights

Acute leukemia (AL) is a hematological malignancy characterized by the uncontrolled proliferation of immature blood cells, disrupting normal hematopoiesis and leading to severe cytopenias and tissue infiltration. In acute myeloid leukemia (AML), leukemic blasts and dysfunctional megakaryocytes replace healthy bone marrow cells, severely impairing platelet production and resulting in thrombocytopenia. This profound reduction in platelet count increases the risk of life-threatening hemorrhagic events, posing a significant challenge in AML management. Beyond their well-established role in hemostasis, platelets actively participate in cancer progression through tumor cell-induced platelet aggregation, which promotes metastasis and immune evasion. By forming microthrombi and secreting a diverse range of bioactive molecules, platelets create a tumor-supportive microenvironment through interactions with endothelial cells, immune cells, fibroblasts, and epithelial cells. These interactions enhance angiogenesis, inflammation, and tumor survival, thereby influencing the pathophysiology of leukemia. Emerging evidence suggests that platelet dysfunction in AML is not merely a consequence of thrombocytopenia but also a key contributor to disease progression. Alterations in platelet signaling, granule secretion, and receptor expression may further exacerbate leukemic cell proliferation and immune evasion. Moreover, platelet-derived extracellular vesicles have been implicated in facilitating leukemic stem cell survival and chemotherapy resistance. This review provides a comprehensive analysis of platelet dysfunction in AML, emphasizing its mechanistic role in disease progression and its potential as a therapeutic target. A deeper understanding of platelet-leukemia crosstalk could reveal novel strategies for mitigating tumor growth and improving patient outcomes. Targeting platelet-mediated pathways may not only enhance conventional leukemia treatments but also pave the way for innovative anti-leukemic therapies with improved efficacy and reduced disease relapse.