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Assessment of regulatory T cells (Tregs) and Foxp3 methylation level in chronic myeloid leukemia patients on tyrosine kinase inhibitor therapy
Immunogenetics ( IF 3.2 ) Pub Date : 2022-12-26 , DOI: 10.1007/s00251-022-01291-4
Shahla'a Fadhil Sabir 1 , Bassam Francis Matti 2, 3 , Wifaq Mahmood Ali Alwatar 4
Affiliation  

The key cell population permits cancer cells to avoid immune-surveillance is regulatory T cells (Tregs). This study evaluates the level of Tregs in chronic myeloid leukemia (CML) patients and the effect of Tyrosine kinase inhibitor (TKI) on Treg levels, as a pathway to understand the immune response and behavior among advance stage and optimal response CML patients using imatinib therapy. Blood samples were collected from 30 CML patients (optimal response to TKI), 30 CML patients (failure response to TKI), and 30 age- and gender-matched controls. Analysis involved measuring percentages of Tregs (CD4 + CD25 + FOXP3 +) by flow cytometer and demethylation levels of FOXP3 Treg-specific demethylated region (TSDR) by PCR. The data revealed that Tregs and the FOXP3-TSDR demethylation percentages significantly increased in failure response group in comparison to the optimal response and control groups, while no significant difference between optimal response and control groups. Tregs and FOXP3 TSDR demethylation percentages showed high sensitivity and specificity, suggesting powerful discriminatory biomarkers between failure and optimal groups. An assessment of the Tregs and demethylation percentage among different BCR-ABL levels of CML patients on TKI revealed no significant differences in parameter percentage in the optimal response to TKI patients with different molecular responses (log 3 reduction or other deeper log 4.5 and 5 reduction levels). Our findings demonstrate an effective role of functional Tregs among different CML stages. Also, the study suggests that the major molecular response to therapy at level 0.1% of BCR-ABL transcript could be enough to induce immune system restoration in patients.



中文翻译:

酪氨酸激酶抑制剂治疗慢性粒细胞白血病患者调节性 T 细胞 (Tregs) 和 Foxp3 甲基化水平的评估

允许癌细胞避开免疫监视的关键细胞群是调节性 T 细胞 (Treg)。本研究评估了慢性粒细胞白血病 (CML) 患者的 Tregs 水平以及酪氨酸激酶抑制剂 (TKI) 对 Treg 水平的影响,作为了解使用伊马替尼治疗的晚期和最佳反应 CML 患者的免疫反应和行为的途径. 从 30 名 CML 患者(对 TKI 的最佳反应)、30 名 CML 患者(对 TKI 的失败反应)和 30 名年龄和性别匹配的对照中采集血样。分析涉及通过流式细胞仪测量 Tregs (CD4 + CD25 + FOXP3 +) 的百分比和通过 PCR 测量 FOXP3 Treg 特异性去甲基化区域 (TSDR) 的去甲基化水平。数据显示,与最佳反应组和对照组相比,失败反应组的 Tregs 和 FOXP3-TSDR 去甲基化百分比显着增加,而最佳反应组和对照组之间没有显着差异。Tregs 和 FOXP3 TSDR 去甲基化百分比显示出高灵敏度和特异性,表明失败组和最佳组之间存在强大的歧视性生物标志物。对接受 TKI 的 CML 患者不同 BCR-ABL 水平的 Tregs 和去甲基化百分比的评估显示,对具有不同分子反应(log 3 减少或其他更深的 log 4.5 和 5 减少水平)的 TKI 患者的最佳反应的参数百分比没有显着差异). 我们的研究结果证明了功能性 Tregs 在不同 CML 阶段中的有效作用。还,

更新日期:2022-12-26
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