Vitamin D and hematologic malignancies: A comprehensive review of its role in therapeutic potential, pathogenesis, and prognosis

Vitamin D has immunomodulatory, anti-proliferative, and pro-differentiative effects that are increasingly linked to hematologic malignancies, beyond its traditional function in maintaining calcium-phosphate balance. Patients with leukemia and lymphoma frequently have vitamin D deficiency, which has been linked to poor prognostic characteristics and a lower chance of survival. The active metabolite 1,25-dihydroxyvitamin D3 stimulates cellular differentiation, suppresses proliferation, and triggers apoptosis in acute leukemias (ALL and AML) by means of vitamin D receptor (VDR)-mediated transcriptional regulation. Based on empirical evidence, a higher tumor burden, a worse response to treatment, and an advanced disease stage are all associated with low vitamin D levels in chronic leukemias (CLL and CML). Similarly, hypovitaminosis D has been associated with worse treatment outcomes for both Hodgkin and non-Hodgkin lymphomas. By modifying cytokine production, immune cell function, angiogenesis, cell cycle regulation, and tumor–microenvironment interactions, vitamin D mechanistically affects leukemogenesis and lymphomagenesis. This review outlines the most recent molecular and clinical data that suggests vitamin D may be used as a prognostic biomarker and an adjuvant therapeutic target in hematologic malignancies. However, to elucidate its therapeutic impact and clinical utility, extensive prospective and randomized studies are needed.