Peking University People's Hospital, Peking University Institute of Hematology, National Clinical Research Center for Hematologic Disease, Beijing, China.
Front Immunol. 2022 Jul 7;13:909104. doi: 10.3389/fimmu.2022.909104. eCollection 2022.
Acute myeloid leukemia (AML) with t(8;21) needs to be further stratified. In addition to leukemia cells, immune cells in tumor microenvironment participate in tumor initiation, growth and progression. Interleukins (ILs)/interleukin receptors (ILRs) interaction plays important roles in the antitumor immune response. IL7R is reported to be relevant to prognosis in solid tumor and acute lymphoblastic leukemia. However, the prognostic significance of IL7R in t(8;21) AML remains to be clarified.
Bone marrows collected from 156 newly diagnosed t(8;21) AML patients were used for testing IL7R transcript level by TaqMan-based real-time quantitative PCR (RQ-PCR), and RNAseq were performed in 15 of them. Moreover, IL7R expression at diagnosis were measured by RQ-PCR and flow cytometry (FCM) simultaneously in other 13 t(8;21) AML patients.
t(8;21) AML patients had varied IL7R transcript levels and were categorized into low-expression (IL7R-L) and high-expression (IL7R-H) groups; IL7R-L was significantly associated with a lower relapse-free survival (RFS) rate (=0.0027) and KIT mutation (=0.0010). Furthermore, IL7R-L was associated with a lower RFS rate in KIT group (=0.013) and IL7R-H/KIT patients had similar RFS to KIT patients (=0.35). GO analysis enrichment showed that down-regulated genes were predominantly involved in the regulation of T cell and leukocyte activation, proliferation and differentiation in IL7R-L group. IL7R-L had significantly lower levels of Granzymes A/B, CCR7, CD28 and CD27 than IL7R-H group (all <0.05). FCM analysis showed IL7R protein was primarily expressed in CD4 T and CD8 T cell subset. A significant association was found between the transcript level of IL7R and the percentage of CD8 T cells in nucleated cells (=0.015) but not CD4 T cells (=0.47).
Low IL7R transcript level of bone marrow at diagnosis predicted relapse in t(8;21) AML, which might be caused by the difference in the amount, status and function of T cells.
伴 t(8;21) 的急性髓系白血病（AML）需要进一步分层。除白血病细胞外，肿瘤微环境中的免疫细胞也参与肿瘤的发生、生长和进展。白细胞介素（ILs）/白细胞介素受体（ILRs）相互作用在抗肿瘤免疫反应中发挥重要作用。IL7R 已被报道与实体瘤和急性淋巴细胞白血病的预后相关。然而，IL7R 在 t(8;21)AML 中的预后意义仍有待阐明。
采用 TaqMan 实时定量 PCR（RQ-PCR）检测 156 例初诊 t(8;21)AML 患者骨髓中 IL7R 转录水平，其中 15 例进行 RNAseq 检测。此外，对其他 13 例 t(8;21)AML 患者同时采用 RQ-PCR 和流式细胞术（FCM）检测诊断时的 IL7R 表达。
t(8;21)AML 患者的 IL7R 转录水平存在差异，分为低表达（IL7R-L）和高表达（IL7R-H）组；IL7R-L 与较低的无复发生存率（RFS）率显著相关（=0.0027）和 KIT 突变（=0.0010）。此外，在 KIT 组中，IL7R-L 与较低的 RFS 率相关（=0.013），而 IL7R-H/KIT 患者的 RFS 与 KIT 患者相似（=0.35）。GO 分析富集表明，下调基因主要参与 IL7R-L 组中 T 细胞和白细胞的激活、增殖和分化的调控。IL7R-L 组的 Granzymes A/B、CCR7、CD28 和 CD27 水平明显低于 IL7R-H 组（均<0.05）。FCM 分析表明，IL7R 蛋白主要表达于 CD4 T 和 CD8 T 细胞亚群。IL7R 转录水平与有核细胞中 CD8 T 细胞的百分比呈显著正相关（=0.015），而与 CD4 T 细胞无相关性（=0.47）。
初诊时骨髓中 IL7R 转录水平较低预示着 t(8;21)AML 复发，这可能是由于 T 细胞数量、状态和功能的差异所致。
