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 percursor cells to enter a genetically determined terminal maturation pathway. The efficacy 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 hematopoietic cells that governs their responsiveness to the antiproliferative/differentiative actions of 1,25(OH)(2)D-3 is outlined. (C) 1997, Elsevier Science Inc.