title: Vitamin D Control of Hematopoietic Cell Differentiation and Leukemia.
abstract: It is now well known that in the mammalian body vitamin D is converted by successive hydroxylations to 1,25-dihydroxyvitamin D (1,25D), a steroid-like hormone with pleiotropic properties. These include important contributions to the control of cell proliferation, survival and differentiation, as well as the regulation of immune responses in disease. Here, we present recent advances in current understanding of the role of 1,25D in myelopoiesis and lymphopoiesis, and the potential of 1,25D and analogs (vitamin D derivatives; VDDs) for the control of hematopoietic malignancies. The reasons for the unimpressive results of most clinical studies of the therapeutic effects of VDDs in leukemia and related diseases may include the lack of a precise rationale for the conduct of these studies. Further, clinical trials to date have generally used extremely heterogeneous patient populations and, in many cases, small numbers of patients, generally without controls. Although low calcemic VDDs have been used and combined with agents that can increase the leukemia cell killing or differentiation effects in acute leukemias, the sequencing of agents used for combination therapy should to be more clearly delineated. Most importantly, it is recommended that in future clinical trials the rationale for the basis of the enhancing action of drug combinations should be clearly articulated and the effects on anticancer immunity should also be evaluated.
authors.affiliation: Department of Pathology & Laboratory Medicine, Rutgers, NJ Medical School, 185 South Orange Ave, Newark, New Jersey 07103.
authors.forename: George P
authors.initials: GP
authors.lastname: Studzinski
authors.affiliation: Department of Medicine, University of Missouri Medical School, One Hospital Drive, Columbia, Missouri 65212.
authors.forename: Jonathan S
authors.initials: JS
authors.lastname: Harrison
authors.affiliation: Department of Pathology & Laboratory Medicine, Rutgers, NJ Medical School, 185 South Orange Ave, Newark, New Jersey 07103.
authors.forename: Xuening
authors.initials: X
authors.lastname: Wang
authors.affiliation: The Huck Institutes of Life Sciences, The Pennsylvania State University, University Park, Pennsylvania 16802.
authors.forename: Surojit
authors.initials: S
authors.lastname: Sarkar
authors.affiliation: The Huck Institutes of Life Sciences, The Pennsylvania State University, University Park, Pennsylvania 16802.
authors.forename: Vandana
authors.initials: V
authors.lastname: Kalia
authors.affiliation: Department of Clinical Biochemistry & Pharmacology, Faculty of Health Sciences, Ben-Gurion University of the Negev, P.O. Box 653, 84105, Beer-Sheva, Israel.
authors.forename: Michael
authors.initials: M
authors.lastname: Danilenko
mesh_terms: D000818:Animals; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000008:administration & dosage / Q000494:pharmacology; D002454:Cell Differentiation / Q000187:drug effects; D002986:Clinical Trials as Topic; D006410:Hematopoiesis / Q000187:drug effects*; D006801:Humans; D007938:Leukemia / Q000188:drug therapy* / Q000473:pathology; D014807:Vitamin D / Q000008:administration & dosage* / Q000031:analogs & derivatives / Q000494:pharmacology; D014815:Vitamins / Q000008:administration & dosage* / Q000494:pharmacology
chemical_list: D014815:Vitamins; D014807:Vitamin D
keywords: CALCITRIOL; HEMATOPOIESIS; LEUKEMIA; VITAMIN D