Studzinski George P, Harrison Jonathan S, Wang Xuening, Sarkar Surojit, Kalia Vandana, Danilenko Michael
Department of Pathology & Laboratory Medicine, Rutgers, NJ Medical School, 185 South Orange Ave, Newark, New Jersey 07103.
Department of Medicine, University of Missouri Medical School, One Hospital Drive, Columbia, Missouri 65212.
J Cell Biochem. 2015 Aug;116(8):1500-12. doi: 10.1002/jcb.25104.
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.
现在众所周知，在哺乳动物体内，维生素D通过连续羟基化转化为1,25 - 二羟基维生素D（1,25D），这是一种具有多效性的类固醇样激素。这些作用包括对细胞增殖、存活和分化控制的重要贡献，以及对疾病中免疫反应的调节。在此，我们阐述了当前对1,25D在骨髓生成和淋巴细胞生成中作用的最新认识进展，以及1,25D及其类似物（维生素D衍生物；VDDs）在控制造血系统恶性肿瘤方面的潜力。VDDs在白血病及相关疾病治疗效果的大多数临床研究结果不佳，其原因可能包括开展这些研究缺乏精确的理论依据。此外，迄今为止的临床试验通常使用极其异质的患者群体，而且在许多情况下，患者数量较少，通常没有对照组。尽管已经使用了低钙血症的VDDs，并与能够增强急性白血病中白血病细胞杀伤或分化作用的药物联合使用，但联合治疗所用药物的顺序应更明确地界定。最重要的是，建议在未来的临床试验中，应明确阐述药物联合增强作用的理论依据，并且还应评估其对抗癌免疫的影响。
