Dizaji Asl Khadijeh, Rafat Ali, Movassaghpour Ali Akbar, Nozad Charoudeh Hojjatollah, Tayefi Nasrabadi Hamid
Student Research Committee, Tabriz University of Medical Sciences, Tabriz, Iran.
Department of Anatomical Sciences, Faculty of Medicine, Tabriz University of Medical Sciences, Tabriz, Iran.
Adv Pharm Bull. 2023 Jan;13(1):170-175. doi: 10.34172/apb.2023.018. Epub 2021 Oct 10.
Acute myeloid leukemia (AML) is known to be an invasive and highly lethal hematological malignancy in adults and children. Resistance to the present treatments, including radiotherapy and chemotherapy with their side effects and telomere length shortening are the main cause of the mortality in AML patients. Telomeres sequence which are located at the end of eukaryotic chromosome play pivotal role in genomic stability. Recent studies have shown that apoptosis process is blocked in AML patient by the excessive telomerase activity in cancerous blasts. Therefore, the find of effective ways to prevent disease progression has been considered by the researchers. Natural killer (NK) cells as granular effector cells play a critical role in elimination of abnormal and tumor cells. Given that the cytotoxic function of NK cells is disrupted in the AML patients, we investigated the effect of telomerase inhibitors on NK cell differentiation. To evaluate telomerase inhibition on NK cell differentiation, the expression of CD105, CD56, CD57, and KIRs was evaluated in CD34 derived NK cells after incubation of them with BIBR1532. The results showed that the expression of CD105, CD56, CD57, and KIRs receptors reduces after telomerase inhibition. According to these findings, BIBR1532 affected the final differentiation of NK cells. The results revealed that telomerase inhibitor drugs suppress cancer cell progression in a NK cells-independent process.
急性髓系白血病（AML）是一种侵袭性强且致死率高的成人和儿童血液系统恶性肿瘤。对包括放疗和化疗及其副作用在内的现有治疗产生耐药性以及端粒长度缩短是AML患者死亡的主要原因。位于真核染色体末端的端粒序列在基因组稳定性中起关键作用。最近的研究表明，AML患者癌细胞中的端粒酶活性过高会阻断凋亡过程。因此，研究人员一直在寻找预防疾病进展的有效方法。自然杀伤（NK）细胞作为颗粒效应细胞，在清除异常细胞和肿瘤细胞方面发挥着关键作用。鉴于AML患者中NK细胞的细胞毒性功能受到破坏，我们研究了端粒酶抑制剂对NK细胞分化的影响。为了评估端粒酶抑制对NK细胞分化的作用，在将CD34衍生的NK细胞与BIBR1532孵育后，评估了CD105、CD56、CD57和杀伤细胞免疫球蛋白样受体（KIRs）的表达。结果表明，端粒酶抑制后，CD105、CD56、CD57和KIRs受体的表达降低。根据这些发现，BIBR1532影响了NK细胞的最终分化。结果显示，端粒酶抑制剂药物在一个不依赖NK细胞的过程中抑制癌细胞进展。
