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自然杀伤细胞激活和抑制性受体在急性髓细胞白血病患者中的基因表达分析。

Gene expression analysis of activating and inhibitory receptors of natural killer cells in patients with acute myeloblastic leukemia.

机构信息

Student Research Committee, Faculty of Allied Medicine, Kerman University of Medical Sciences, Kerman, Iran.

Department of Hematology and Oncology, Faculty of Medicine, Kerman University of Medical Sciences, Kerman, Iran.

出版信息

Adv Med Sci. 2020 Sep;65(2):354-360. doi: 10.1016/j.advms.2020.05.007. Epub 2020 Jun 24.

DOI:10.1016/j.advms.2020.05.007
PMID:32592956
Abstract

PURPOSE

Natural killer (NK) cells are cytotoxic lymphocytes, which have long been known to play an essential role in immune surveillance of tumor cells. The results of several clinical studies imply evidence of impaired activity of NK cells in acute myeloblastic leukemia (AML). The aim of this study was to investigate the gene expression of activating and inhibitory receptors of NK cells in patients with newly diagnosed AML before and after induction therapy using 7 + 3 regimen in comparison to healthy donors.

MATERIALS AND METHODS

Sixteen AML patients aged 16-64 years as well as 16 matched healthy individuals were studied. Peripheral blood samples from patients were obtained in two steps, namely, in newly diagnosed patients and 28 days after receiving induction therapy. Real-time PCR was performed to evaluate the expression levels of activating receptors, including DNAM-1 and NKp46 as well as inhibitory receptors of KIR2DL1 and NKG2A.

RESULTS

Our results demonstrated that the newly diagnosed patients showed over 50% decrease in NKp46 expression and a 6-fold increase in KIR2DL1 expression compared to healthy controls. The mRNA expression analysis in patients after induction therapy suggested a significant decrease in mRNA expressions of KIR2DL1 and NKG2A in comparison to newly diagnosed patients.

CONCLUSION

Herewith, we show a statistical difference in mRNA expression levels of activating (NKp46) and inhibitory receptors from NK cells in newly diagnosed AML patients when compared with healthy controls or patients who received induction therapy, supporting the findings of researchers who reported the impaired NK cells cytotoxicity in AML patients.

摘要

目的

自然杀伤 (NK) 细胞是细胞毒性淋巴细胞,长期以来一直被认为在肿瘤细胞的免疫监视中发挥着重要作用。几项临床研究的结果表明,急性髓细胞白血病 (AML) 患者 NK 细胞的活性受损。本研究旨在使用 7+3 方案比较新诊断的 AML 患者在诱导治疗前后与健康供体相比,研究 NK 细胞的激活和抑制受体的基因表达。

材料和方法

研究了 16 名年龄在 16-64 岁的 AML 患者和 16 名匹配的健康个体。患者的外周血样本分两步获得,即在新诊断的患者中和接受诱导治疗 28 天后获得。实时 PCR 用于评估激活受体(包括 DNAM-1 和 NKp46)和抑制受体 KIR2DL1 和 NKG2A 的表达水平。

结果

我们的结果表明,与健康对照组相比,新诊断的患者 NKp46 表达降低了 50%以上,而 KIR2DL1 表达增加了 6 倍。诱导治疗后患者的 mRNA 表达分析表明,与新诊断的患者相比,KIR2DL1 和 NKG2A 的 mRNA 表达显著降低。

结论

在此,我们显示了新诊断的 AML 患者与健康对照组或接受诱导治疗的患者相比,NK 细胞激活(NKp46)和抑制受体的 mRNA 表达水平存在统计学差异,支持了研究人员报告的 AML 患者 NK 细胞细胞毒性受损的发现。

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