Department of Hematology, First Affiliated Hospital, Institute of Hematology, School of Medicine, Key Laboratory for Regenerative Medicine of Ministry of Education, Jinan University, Guangzhou, People's Republic of China.
Guangzhou Municipality Tianhe Nuoya Bio-engineering Co. Ltd, Guangzhou, People's Republic of China.
Hematology. 2022 Dec;27(1):523-529. doi: 10.1080/16078454.2022.2066245.
T cell dysfunction is a common characteristic of patients with myeloid leukemia and is closely related to clinical efficacy and prognosis. In order to clarify the mechanisms leading to the T cell dysfunction, we characterized the gene expression profile of T cells from chronic myelogenous leukemia (CML) patients by microarray analysis and investigated the related regulating pathway.
We employed gene expression profiling, bioinformatics and real-time quantitative reverse transcription PCR (RT-qPCR) to detect genes differentially expressed in CML patients versus healthy donors.
There were 1704 genes differentially expressed between CD3 T cells from CML patients and healthy donors, including 868 up-regulated genes and 836 down-regulated genes, which mostly related to T cell functional pathways. In particular, lower expression of , a member of the TCR signaling pathway, was detected in CD3 T cells from CML patients. We further found that the expression of and , transcription factors that potentially regulate , in CD3 T cells from CML patients was significantly lower than that in healthy donors.
We for the first time observed the altered gene expression profiles of CD3 T cells from CML patients, and the results suggested that , and may be involved in regulating T cell dysfunction in CML patients in the form of a transcriptional regulatory network. These findings may provide potential targets for tyrosine kinase inhibitors in combination with other targeted immunotherapies .
T 细胞功能障碍是髓系白血病患者的一个常见特征，与临床疗效和预后密切相关。为了阐明导致 T 细胞功能障碍的机制，我们通过微阵列分析对慢性髓系白血病（CML）患者的 T 细胞基因表达谱进行了特征描述，并研究了相关的调节途径。
我们采用基因表达谱分析、生物信息学和实时定量逆转录 PCR（RT-qPCR）检测 CML 患者与健康供体 T 细胞中差异表达的基因。
CML 患者和健康供体的 CD3 T 细胞之间有 1704 个基因表达差异，包括 868 个上调基因和 836 个下调基因，这些基因主要与 T 细胞功能途径相关。特别是，在 CML 患者的 CD3 T 细胞中，T 细胞受体信号通路的成员 的表达水平较低。我们进一步发现，CML 患者的 CD3 T 细胞中，转录因子 和 的表达水平明显低于健康供体，它们可能潜在地调节 。
我们首次观察到 CML 患者 CD3 T 细胞的基因表达谱发生改变，结果表明， 、 和 可能以转录调控网络的形式参与调节 CML 患者的 T 细胞功能障碍。这些发现可能为酪氨酸激酶抑制剂与其他靶向免疫疗法联合治疗提供潜在靶点。
