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未经治疗的骨髓增生异常综合征患者造血干细胞中 TIM3+的升高显示出异常分化、过度增殖和凋亡减少。

Elevated TIM3+ hematopoietic stem cells in untreated myelodysplastic syndrome displayed aberrant differentiation, overproliferation and decreased apoptosis.

机构信息

Department of Hematology, General Hospital of Tianjin Medical University, Tianjin 300052, China.

Department of Hematology, General Hospital of Tianjin Medical University, Tianjin 300052, China.

出版信息

Leuk Res. 2014 Jun;38(6):714-21. doi: 10.1016/j.leukres.2014.03.018. Epub 2014 Apr 1.

Abstract

TIM3, as a negative regulator of anti-tumor immunity, is highly expressed on LSCs, but not on normal HSCs. TIM3 on HSCs in MDS patients has not been clarified. Here, both the percentage of TIM3 on HSCs and the MFI of TIM3+ HSCs were higher in untreated MDS than control and were closed to AML, and excessive TIM3+ HSCs was closely related to clinical parameters: WPSS score, karyotype analysis, morphologic blasts, the number of cytopenia involving hematopoietic lineages, anemia and granulocytopenia. TIM3+ HSCs expressed lower CD11b, TpoR, EpoR, G-CSFR and Annexin V, and higher CD71 and GATA2. TIM3+ HSCs displayed aberrant differentiation, overproliferation and decreased apoptosis. TIM3 might be a promising marker for identifying malignant clone cells in MDS and a candidate for targeted therapy.

摘要

TIM3 作为抗肿瘤免疫的负调节剂,在 LSCs 上高度表达,但在正常 HSCs 上不表达。MDS 患者 HSCs 上的 TIM3 尚未阐明。在这里,未经治疗的 MDS 患者 HSCs 上 TIM3 的百分比和 TIM3+ HSCs 的 MFI 均高于对照组且接近 AML,并且过多的 TIM3+ HSCs 与临床参数密切相关:WPSS 评分、细胞遗传学分析、形态学原始细胞、涉及造血谱系的血细胞减少的数量、贫血和粒细胞减少。TIM3+ HSCs 表达较低的 CD11b、TpoR、EpoR、G-CSFR 和 Annexin V,而表达较高的 CD71 和 GATA2。TIM3+ HSCs 表现出异常分化、过度增殖和减少凋亡。TIM3 可能是 MDS 中识别恶性克隆细胞的有前途的标志物,也是靶向治疗的候选标志物。

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