Therapeutic implications of vitamin D in leukemia: mechanistic and clinical perspectives

Recent research has highlighted vitamin D's potential role in the development and treatment of hematological cancers, expanding its known importance beyond calcium regulation and bone health. Patients with blood disorders often exhibit lower serum concentrations of 25(OH)D3, the precursor to calcitriol (1,25(OH)₂D3, active form of vitamin D), compared to healthy individuals. This deficiency frequently correlates with worse disease outcomes. Additionally, cells affected by these disorders typically show elevated expression of the vitamin D receptor (VDR), which is crucial for many of the observed anti-cancer effects in various experimental models. Supplementation with vitamin D in abnormal blood cells has been shown to encourage cell death, stimulate differentiation, curb proliferation, enhance tumor cell sensitivity to other cancer therapies, and decrease the production of inflammatory cytokines. While the doses required to achieve these effects may lead to hypercalcemia in humans, researchers have developed analogs and combination treatments to mitigate this side effect. These findings underscore the importance of continued research into the role of vitamin D in hematological cancers and its potential as a therapeutic agent or adjuvant in treatment strategies. This review evaluates the role of vitamin D in leukemia by synthesizing mechanistic, clinical, and epidemiological evidence, with the aim of clarifying its prognostic value and therapeutic potential in precision medicine.