Pd-1 和 Tim-3 的免疫检查点基因表达在急性髓性白血病患者中的作用

Sara Mohammed Oudah, I. H. Hamzah, B. Matti
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摘要

急性髓性白血病(AML)是一种造血细胞癌,会迅速扩散到血液中,并在骨髓中迅速发展。尽管最近治疗手段有所改善,但急性髓性白血病(AML)患者的预后仍然很差。在血液恶性肿瘤中,免疫检查点抑制剂已被研究,如急性髓性白血病;然而,程序性细胞死亡-1(PD-1)和T细胞免疫球蛋白和粘蛋白结构域3(TIM3)在急性髓性白血病中的作用尚未被彻底阐明。因此,本研究旨在调查急性髓细胞性白血病患者的 PD-1 和 TIM-3 基因表达,并确定其与临床结果和预后变量的关系。研究收集了80份急性髓性白血病(AML)患者的血液样本,并评估了40份健康志愿者的血液样本作为对照,对PD-1和TIM-3的表达进行了实时定量(qRT-PCR)分析。结果显示,急性髓细胞白血病患者中 TIM-3 的表达无显著性差异(P>0.0001),而 PD-1 的表达在统计学上有高度显著性差异(P ≤ 0.0001)。患者与对照组的 PD-1 临界值(0.853)比患者与对照组的 TIM-3 临界值灵敏度高,在区分患者与对照组方面具有诊断意义。我们的数据结果表明,T 细胞中 PD-1 的高表达与急性髓细胞性白血病患者的疾病进展和 TIM-3 基因表达下调有极大的相关性。
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The Role of Immune Check Point Gene Expression of Pd-1 and Tim-3 in Patients with Acute Myeloid Leukemia
Acute myeloid leukemia (AML) is a hematopoietic cell cancer that spreads quickly to the blood and rapidly developing in the bone marrow. The prognosis for patients with acute myeloid leukemia (AML) is still poor, despite recent improvements in the therapeutic landscape. In hematological malignancies, immune checkpoint inhibitors have been studied, such as AML; however, the role of program cell death -1(PD-1) and T-cell immunoglobulin and mucin domain 3 (TIM3) in AML has not been thoroughly elucidated yet. Thus, the current study conducted to investigate the PD-1 and TIM‑3 gene expression in the AML patients and determine its associations with clinical outcomes and prognostic variables. The study collected 80 blood samples from acute myeloid leukemia (AML) patients and 40 blood samples from volunteer healthy individual were evaluated as control and real time quantitative (qRT-PCR) analysis was detect to performed PD-1 and TIM‑3 expression. The result showed there was non-significant (P>0.0001) in expression of TIM-3 in patients with AML, while expression of PD-1 statistically has high significant difference (P ≤ 0.0001). A cutoff value of PD-1 for patients vs. control was (0.853) with high sensitivity than cutoff value of TIM-3 for patients vs. control that can be diagnostically significant in distinguishing between patients and controls. Our data result showed that high expression of PD-1 in T cell is extremely correlated with progression of disease and down regulated gene expression of TIM-3 in AML patients.
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