Department of Biotechnology, University of Wrocław, Joliot-Curie 14a, 50-383 Wrocław, Poland.
Faculty of Mathematics and Computer Science, University of Wrocław, Joliot-Curie 15, 50-383 Wrocław, Poland.
Int J Mol Sci. 2023 Mar 30;24(7):6504. doi: 10.3390/ijms24076504.
(1) Hematological malignancies are characterized by an immortalization, uncontrolled proliferation of blood cells and their differentiation block, followed by the loss of function. The primary goal in the treatment of leukemias is the elimination of rapidly proliferating leukemic cells (named blasts). However, chemotherapy, which removes proliferating blasts, also prevents the remaining immune cells from being activated. Acute leukemias affect elderly people, who are often not fit to survive aggressive chemotherapy. Therefore, there is a need of milder treatment, named differentiation therapy, which might simulate the immune system of the patient. 1,25-Dihydroxyvitamin D, or low-calcemic analogs of this compound, were proposed as supporting therapy in acute leukemias. (2) Bone marrow blasts from patients with hematological malignancies, and leukocytes from healthy volunteers were ex vivo exposed to 1,25-dihydroxyvitamin D, and then their genomes and transcriptomes were investigated. (3) Our analysis indicates that 1,25-dihydroxyvitamin D regulates in blood cells predominantly genes involved in immune response, such as (cathelicidin antimicrobial peptide), (ceruloplasmin), (C-X-C motif chemokine ligand 9), (CD14 molecule) or (vitelline membrane outer layer 1 homolog). This concerns blood cells from healthy people, as well as blasts from patients with hematological malignancies. In addition, in one patient, 1,25-dihydroxyvitamin D significantly downregulated transcription of genes responsible for cell division and immortalization. (4) In conclusion, the data presented in this paper suggest that addition of 1,25-dihydroxyvitamin D to the currently available treatments would stimulate immune system, inhibit proliferation and reduce immortal potential of blasts.
（1）血液系统恶性肿瘤的特征是血细胞的永生化、不受控制的增殖及其分化阻断，随后功能丧失。白血病治疗的主要目标是消除快速增殖的白血病细胞（称为白血病细胞）。然而，去除增殖性白血病细胞的化疗也会阻止剩余的免疫细胞被激活。急性白血病影响老年人，他们通常不适合接受强烈的化疗。因此，需要更温和的治疗方法，称为分化疗法，它可能模拟患者的免疫系统。1,25-二羟维生素 D 或这种化合物的低钙类似物被提议作为急性白血病的辅助治疗。（2）来自血液系统恶性肿瘤患者的骨髓白血病细胞和来自健康志愿者的白细胞在体外暴露于 1,25-二羟维生素 D，然后研究它们的基因组和转录组。（3）我们的分析表明，1,25-二羟维生素 D 在血液细胞中主要调节参与免疫反应的基因，如（抗菌肽 cathelicidin）、（铜蓝蛋白）、（C-X-C 基序趋化因子配体 9）、（CD14 分子）或（卵黄膜外层 1 同源物）。这涉及来自健康人的血细胞，以及来自血液系统恶性肿瘤患者的白血病细胞。此外，在一名患者中，1,25-二羟维生素 D 显著下调了负责细胞分裂和永生化的基因的转录。（4）总之，本文提供的数据表明，在现有治疗方法的基础上添加 1,25-二羟维生素 D 将刺激免疫系统，抑制增殖并降低白血病细胞的永生化潜力。
