Department of Biotechnology, University of Wroclaw, Joliot-Curie 14a, 50-383 Wroclaw, Poland.
Nutrients. 2022 Jul 12;14(14):2851. doi: 10.3390/nu14142851.
Acute myeloid leukemia (AML) is an aggressive and often fatal hematopoietic malignancy. A very attractive way to treat myeloid leukemia, called "differentiation therapy", was proposed when in vitro studies showed that some compounds are capable of inducing differentiation of AML cell lines. One of the differentiation-inducing agents, all--retinoic acid (ATRA), which can induce granulocytic differentiation in AML cell lines, has been introduced into clinics to treat patients with acute promyelocytic leukemia (APL) in which a PML-RARA fusion protein is generated by a chromosomal translocation. ATRA has greatly improved the treatment of APL. Since 1,25-dihydroxyvitamin D (1,25D) is capable of inducing monocytic differentiation of leukemic cells, the idea of treating other AMLs with vitamin D analogs was widely accepted. However, early clinical trials in which cancer patients were treated either with 1,25D or with analogs did not lead to conclusive results. Recent results have shown that AML types with certain mutations, such as isocitrate dehydrogenase (IDH) mutations, may be the right targets for differentiation therapy using 1,25D, due to upregulation of vitamin D receptor (VDR) pathway.
急性髓系白血病（AML）是一种侵袭性且常致命的血液系统恶性肿瘤。当体外研究表明某些化合物能够诱导 AML 细胞系分化时，提出了一种非常有吸引力的治疗髓系白血病的方法，称为“分化疗法”。一种分化诱导剂，全反式维甲酸（ATRA），能够诱导 AML 细胞系向粒细胞分化，已被引入临床用于治疗由染色体易位产生 PML-RARA 融合蛋白的急性早幼粒细胞白血病（APL）。ATRA 极大地改善了 APL 的治疗效果。由于 1,25-二羟维生素 D（1,25D）能够诱导白血病细胞的单核细胞分化，用维生素 D 类似物治疗其他 AML 的想法被广泛接受。然而，早期的临床试验表明，癌症患者接受 1,25D 或类似物治疗并没有得出明确的结果。最近的研究结果表明，由于维生素 D 受体（VDR）途径的上调，某些突变（如异柠檬酸脱氢酶（IDH）突变）的 AML 类型可能是使用 1,25D 进行分化治疗的合适靶点。
