Vitamin D in hematological disorders and malignancies

Abstract

Commonly known for its critical role in calcium homeostasis and bone mineralization, more recently vitamin D has been implicated in hematological cancer pathogenesis and shows promise as an anti-cancer therapy. Serum levels of 25(OH)D₃ , the precursor to the active form of vitamin D, calcitriol, are frequently lower in patients with hematological disease compared to healthy individuals. This often correlates with worse disease outcome. Furthermore, diseased cells typically highly express the vitamin D receptor, which is required for many of the anti-cancer effects observed in multiple in vivo and in vitro cancer models. In abnormal hematological cells, vitamin D supplementation promotes apoptosis, induces differentiation, inhibits proliferation, sensitizes tumor cells to other anti-cancer therapies, and reduces the production of pro-inflammatory cytokines. Although the dosage of vitamin D required to achieve these effects may induce hypercalcemia in humans, analogs and combinatorial treatments have been developed to circumvent this side effect. Vitamin D and its analogs are well tolerated in clinical trials, and thus, further investigation into the use of these agents in the clinic is warranted. Here, we review the current literature in this field.

Keywords: 25(OH)D3; aplastic anemia; calcitriol; immune cells; leukemia; lymphoma; vitamin D; vitamin D receptor.

Figure 1

Visual representation of polymorphisms discussed in this review. Figure was captured from the UCSC genome browser (https://genome.ucsc.edu) utilizing the GRCh37/hg19 human genome assembly. Chromosome cytoband, chromosome coordinates and relative position of exons (wide bars), introns (line with arrow) and untranslated regions (narrow bars) of four isoforms of the VDR are shown. Eight germline SNPs are noted.

Figure 2

Summary of anti-cancer actions of vitamin D in haematological disorders and malignancies as described in the review. See text for references.