Ferroptosis in Hematological Diseases: Malignant Vulnerabilities and Normal Hematopoietic Protection

Ferroptosis is an iron-dependent form of regulated cell death associated with the accumulation of damaging lipid peroxides. Its relevance to hematological disease is bidirectional: inducing ferroptosis may expose vulnerabilities in malignant cells, whereas preventing it may protect erythroid cells, hematopoietic stem cells and iron-handling macrophages. Evidence was assessed across lipid composition, glutathione-GPX4 signaling, FSP1-dependent defenses and iron handling in leukemia, lymphoma, myeloma, disordered erythropoiesis and marrow injury. Experimental studies identify promising combinations with existing anticancer strategies, but most findings derive from cell systems, animal models or patient-derived material rather than comparative clinical trials. Iron overload and transfusion-related erythrophagocytosis provide additional contexts in which ferroptotic injury may contribute to pathology. Translation requires functional confirmation of ferroptosis, selective delivery and assessment of normal hematopoietic toxicity. A molecular signature or oxidative-stress measurement alone is insufficient to establish ferroptotic death or justify a therapeutic claim.