Munker R, Zhang W, Elstner E, Koeffler H P
Medizinische Klinik III der LMU (Klinikum Grosshadern) Munich, Germany.
Leuk Lymphoma. 1998 Oct;31(3-4):279-84. doi: 10.3109/10428199809059220.
Vitamin D compounds induce differentiation of human leukemic cells and have potential for the treatment of leukemia. In this review we summarize some of the basic mechanisms underlying the action of vitamin D compounds. A variety of vitamin D analogues were synthesized until now, some of which have enhanced antileukemic activity and a decreased propensity to cause hypercalcemia. Most actions of vitamin D compounds are mediated by nuclear receptors. In vivo, vitamin D binding protein interacts with free vitamin D compounds. Both in normal and leukemic cells, vitamin D compounds cause a differentiation to monocytes and macrophages. A variety of genes are regulated by vitamin D compounds. Recently, the cell cycle inhibitory gene p21/WAF-1/CIP-1 was characterized. The expression de novo of WAF-1 in blasts of acute myelogenous leukemia is an independent factor of unfavorable prognosis. In HL-60 leukemic cells treated with vitamin D analogs, WAF-1 can be induced by nano- or picomolar concentrations of vitamin D analogs and correlates with the induction of a differentiated phenotype. When vitamin D analogs are combined in-vitro with retinoids, an irreversible differentiation is observed. Clinical trials of vitamin D analogs are indicated in the situation of minimal residual disease and in combination with standard chemotherapy.
维生素D化合物可诱导人白血病细胞分化，具有治疗白血病的潜力。在本综述中，我们总结了维生素D化合物作用的一些基本机制。到目前为止，已合成了多种维生素D类似物，其中一些具有增强的抗白血病活性和降低的引起高钙血症的倾向。维生素D化合物的大多数作用是由核受体介导的。在体内，维生素D结合蛋白与游离维生素D化合物相互作用。在正常细胞和白血病细胞中，维生素D化合物均可诱导细胞分化为单核细胞和巨噬细胞。多种基因受维生素D化合物调控。最近，细胞周期抑制基因p21/WAF-1/CIP-1得到了表征。急性髓性白血病原始细胞中WAF-1的从头表达是不良预后的独立因素。在用维生素D类似物处理的HL-60白血病细胞中，纳摩尔或皮摩尔浓度的维生素D类似物可诱导WAF-1表达，且与分化表型的诱导相关。当维生素D类似物在体外与维甲酸联合使用时，可观察到不可逆的分化。维生素D类似物的临床试验适用于微小残留病情况以及与标准化疗联合使用的情况。
