Vitamin D and Hematopoiesis

Analysis of the nonclassic actions of vitamin D(3) has highlighted a wide range of target tissues for the hormone 1,25-dihydroxyvitamin D(3) [1,25(OH)(2)D(3)]. Systemic or locally produced 1,25(OH)(2)D(3) may play a role in modulating cell development processes such as hematopoiesis. The mechanisms by which 1,25(OH)(2)D(3) achieves this are discussed in this review. In particular, data from our laboratories suggest that 1,25(OH)(2)D(3) does not provide a deterministic signal for monocyte differentiation. Rather, the hormone acts as a permissive agent for myeloid precursor cells to enter a genetically determined terminal maturation pathway. The effiacy of 1,25(OH)(2)D(3) in leukemia therapy has been improved by the development of novel vitamin D analogues that have potent antiproliferative activity and low hypercalcemic side effects. Another solution to the problem of side effects is to enhance specifically the antiproliferative effects of 1,25(OH)(2)D(3). A novel mechanism within hematopoiesic cells that governs their responsiveness to the antiproliferative/differentiative actions of 1,25(OH)(2)D(3) outlined.