Mechanistic Insights into the Therapeutic Role of Curcumin in Leukemia: Molecular Targets and Clinical Implications

Leukemia is one of the most widespread and life-threatening malignancies that originates in the blood and bone marrow. Despite advances in treatment, there remains a need for safer and more effective therapeutic agents with fewer side effects. This review investigates the therapeutic potential of curcumin (CUR), a naturally derived polyphenol, in leukemia management, with a focus on its molecular mechanisms and regulatory effects on various signaling pathways. Peer-reviewed publications were considered till March 2025. Various scientific databases, including PubMed, Scopus, Science Direct, SciFinder, Medline, and Google Scholar, were used to collect the literature knowledge. The review focuses on the role of curcumin in modulating key cellular processes, such as apoptosis, cell cycle arrest, and gene regulation, along with its interaction with several oncogenic and protective signaling cascades. Accordingly, CUR demonstrates potent antileukemic effects by promoting apoptosis and cell cycle arrest. It downregulates oncogenes, such as FLT3, Akt, ROS, and NF-κB, while protecting normal cells through upregulation of NRF-2, which enhances antioxidant production. Additionally, CUR modulates multiple signaling pathways, including NF-κB, JAK/STAT, PI3K/AKT, JNK/ERK, MAPK, Ras/Raf, and MMP, thereby affecting leukemia initiation, progression, and metastasis. CUR exhibits strong potential as a therapeutic agent for leukemia by targeting multiple molecular signaling pathways and promoting selective cytotoxicity against cancer cells. Further preclinical and clinical studies are necessary to validate its efficacy and overcome the limitations of the bioavailability parameters.