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After Treatment Decrease of Bone Marrow Tregs and Outcome in Younger Patients with Newly Diagnosed Acute Myeloid Leukemia
Journal of Immunology Research ( IF 3.5 ) Pub Date : 2020-11-04 , DOI: 10.1155/2020/2134647
Mario Delia 1 , Paola Carluccio 1 , Anna Mestice 1 , Roberta Frappampina 1 , Francesco Albano 1 , Giorgina Specchia 2 , Pellegrino Musto 1
Affiliation  

An emerging body of evidence demonstrates that defects in antileukemic effector cells in patients with acute myeloid leukemia (AML) can contribute to the development and/or persistence of the disease. In particular, immune suppressive regulatory T cells (Tregs) may contribute to this defective antileukemic immune response, being recruited by bone marrow leukemic cells to evade immune surveillance. We evaluated Tregs (CD4+/CD45RA-/CD25high/CD127low), performing multiparametric flow cytometry on freshly collected bone marrow aspirate (BMA), in addition to the usual molecular and cytogenetic work-up in newly diagnosed AML patients to look for any correlation between Tregs and the overall response rate (ORR). We studied 39 AML younger patients (<65 years), all treated with standard induction chemotherapy. ORR (complete remission (CR)+CR with incomplete hematologic recovery (CRi)) was documented in 21 out of 39 patients (54%); two partial responder patients were also recorded. Apart from the expected impact of the molecular-cytogenetic group () and the NPM mutation (), diagnostic BMA Tregs did not show any correlation with ORR. However, although BMA Tregs did not differ in the study population after treatment, their counts significantly decreased in responder patients (), while no difference was documented in nonresponder ones. This suggested that the removal of Treg cells is able to evoke and enhance anti-AML immune response. However, the role of BMA Tregs in mediating immune system-AML interactions in the diagnostic and posttreatment phase should be confirmed in a greater number of patients.

中文翻译:


新诊断的急性髓系白血病年轻患者治疗后骨髓 Tregs 的减少和结果



大量证据表明,急性髓系白血病 (AML) 患者的抗白血病效应细胞缺陷可能导致疾病的发展和/或持续存在。特别是,免疫抑制性调节性 T 细胞 (Treg) 可能会导致这种有缺陷的抗白血病免疫反应,它们被骨髓白血病细胞招募来逃避免疫监视。我们评估了 Tregs(CD4+/CD45RA-/CD25/CD127),除了对新诊断的 AML 患者进行常规分子和细胞遗传学检查外,还对新鲜收集的骨髓抽吸物 (BMA) 进行多参数流式细胞术,以寻找是否存在任何异常。 Tregs 与总体缓解率 (ORR) 之间的相关性。我们研究了 39 名 AML 年轻患者 (<65 id=2> 和 NPM 突变( ),诊断性 BMA Tregs 未显示与 ORR 任何相关性。然而,尽管治疗后研究人群中的 BMA Tregs 没有差异,但在有反应的患者中,它们的计数显着下降( ),而无反应者中没有记录到差异。这表明Treg细胞的去除能够激发并增强抗AML免疫反应。 然而,BMA Tregs 在诊断和治疗后阶段介导免疫系统-AML 相互作用中的作用应该在更多患者中得到证实。
更新日期:2020-11-04
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