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细胞毒性T淋巴细胞通过抑制Bcl-2表达促进阿糖胞苷诱导的急性髓系白血病细胞凋亡。

Cytotoxic T lymphocytes promote cytarabine-induced acute myeloid leukemia cell apoptosis via inhibiting Bcl-2 expression.

作者信息

Deng Rui, Fan Fang-Yi, Yi Hai, Fu Li, Zeng Yan, Wang Yi, Miao Xiao-Juan, Shuai Yan-Rong, He Guang-Cui, Su Yi

机构信息

Department of Hematology and Hematopoietic Stem Cell Transplantation, Chengdu Military General Hospital of the People's Liberation Army, Chengdu, Sichuan 610083, P.R. China.

出版信息

Exp Ther Med. 2017 Aug;14(2):1081-1085. doi: 10.3892/etm.2017.4620. Epub 2017 Jun 16.

DOI:10.3892/etm.2017.4620
PMID:28810561
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC5526043/
Abstract

Acute myeloid leukemia (AML) remains difficult to cure due to its drug tolerance and refractoriness. Immunotherapy is a growing area of cancer research, which has been applied for the treatment of numerous types of cancer, including leukemia. The present study generated AML cell-specific cytotoxic T lymphocytes (CTLs) and investigated the effect of combining CTL treatment with one of the most commonly used drugs for the treatment of hematological malignancies, cytarabine, on AML cell apoptosis. Firstly, it was observed that monocyte-depleted peripheral blood lymphocytes from healthy donors could be used to generate large numbers of CD3CD8 CTLs through immune stimulation. These CD3CD8 CTLs could effectively recognize and induce the apoptosis of human Kasumi-3 AML cells. In addition, cytarabine-induced AML cell apoptosis was enhanced by CTL treatment. Western blotting revealed that Bcl-2 expression was downregulated in AML cells following cytarabine and CTL treatment, indicating that the synergistic effect of this treatment on AML cell apoptosis is due to the downregulation of Bcl-2. These results highlight the potential application of CTL immunotherapy for the treatment of AML. Further studies optimizing the specificity and potency of CTLs, and identifying favorable combinations with other chemotherapeutic drug are required.

摘要

急性髓系白血病(AML)因其耐药性和难治性而仍然难以治愈。免疫疗法是癌症研究中一个不断发展的领域,已被应用于多种癌症的治疗,包括白血病。本研究生成了AML细胞特异性细胞毒性T淋巴细胞(CTLs),并研究了将CTL治疗与治疗血液系统恶性肿瘤最常用的药物之一阿糖胞苷联合应用对AML细胞凋亡的影响。首先,观察到来自健康供体的单核细胞耗竭外周血淋巴细胞可通过免疫刺激用于生成大量CD3CD8 CTLs。这些CD3CD8 CTLs能够有效识别并诱导人Kasumi-3 AML细胞凋亡。此外,CTL治疗增强了阿糖胞苷诱导的AML细胞凋亡。蛋白质印迹法显示,阿糖胞苷和CTL治疗后,AML细胞中Bcl-2表达下调,表明这种治疗对AML细胞凋亡的协同作用是由于Bcl-2的下调。这些结果突出了CTL免疫疗法在AML治疗中的潜在应用。需要进一步研究优化CTL的特异性和效力,并确定与其他化疗药物的有利联合。

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