Malondialdehyde at the Crossroads of Oxidative Stress, Lipid Peroxidation, Ferroptosis, and Hematological Malignancies: A Narrative Review.
Key claim: Malondialdehyde is consistently elevated in Philadelphia-negative MPNs and other hematological malignancies and tracks oxidative stress, disease activity, thrombosis risk, treatment resistance, and ferroptosis-related lipid peroxidation.
Abstract
Oxidative stress is increasingly recognized as a key contributor to the biology of hematological malignancies. Excessive production of reactive oxygen species disrupts redox homeostasis, promotes genomic instability, alters cellular signaling pathways, and influences disease progression, therapeutic response, and resistance mechanisms. Among the downstream consequences of oxidative stress, lipid peroxidation represents a major source of cellular injury, generating reactive aldehydes capable of amplifying molecular damage. Malondialdehyde, a stable end product of lipid peroxidation, has emerged as one of the most widely investigated biomarkers of oxidative damage in hematologic cancers. This review summarizes current evidence regarding the role of malondialdehyde across major hematological malignancies, including acute and chronic myeloid leukemias, Philadelphia-negative myeloproliferative neoplasms, lymphomas, and multiple myeloma. Available evidence consistently demonstrates significantly elevated MDA levels across major hematological malignancies, including acute and chronic myeloid leukemias, Philadelphia-negative myeloproliferative neoplasms, lymphomas, and multiple myeloma. Increased MDA concentrations are frequently associated with disease activity, relapse, impaired antioxidant defenses, thrombotic complications, treatment resistance, and therapy-related toxicity. Furthermore, experimental studies indicate that MDA accumulation closely parallels ferroptosis induction and may serve as a pharmacodynamic marker of lipid peroxide-mediated cell death. Overall, the reviewed literature identifies MDA as one of the most consistent biomarkers of oxidative stress and lipid peroxidation in hematological cancers. Although methodological standardization remains necessary, MDA appears to have potential diagnostic, prognostic, and therapeutic relevance and may contribute to identifying redox vulnerabilities that can be exploited by emerging ferroptosis-based treatment strategies.
Why this matters
Malondialdehyde is consistently elevated in Philadelphia-negative MPNs and other hematological malignancies and tracks oxidative stress, disease activity, thrombosis risk, treatment resistance, and ferroptosis-related lipid peroxidation.