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揭示靶向慢性粒细胞白血病干细胞的奥秘

Shedding Light on Targeting Chronic Myeloid Leukemia Stem Cells.

作者信息

Houshmand Mohammad, Kazemi Alireza, Anjam Najmedini Ali, Ali Muhammad Shahzad, Gaidano Valentina, Cignetti Alessandro, Fava Carmen, Cilloni Daniela, Saglio Giuseppe, Circosta Paola

机构信息

Department of Clinical Biological Sciences, University of Turin, San Luigi University Hospital, 10043 Turin, Italy.

Department of Hematology and Blood Banking, School of Allied Medical Sciences, Shahid Beheshti University of Medical Sciences, Tehran 1971653313, Iran.

出版信息

J Clin Med. 2021 Dec 11;10(24):5805. doi: 10.3390/jcm10245805.

Abstract

Chronic myeloid leukemia stem cells (CML LSCs) are a rare and quiescent population that are resistant to tyrosine kinase inhibitors (TKI). When TKI therapy is discontinued in CML patients in deep, sustained and apparently stable molecular remission, these cells in approximately half of the cases restart to grow, resuming the leukemic process. The elimination of these TKI resistant leukemic stem cells is therefore an essential step in increasing the percentage of those patients who can reach a successful long-term treatment free remission (TFR). The understanding of the biology of the LSCs and the identification of the differences, phenotypic and/or metabolic, that could eventually allow them to be distinguished from the normal hematopoietic stem cells (HSCs) are therefore important steps in designing strategies to target LSCs in a rather selective way, sparing the normal counterparts.

摘要

慢性粒细胞白血病干细胞(CML LSCs)是一种罕见且静止的细胞群体,对酪氨酸激酶抑制剂(TKI)具有抗性。当处于深度、持续且明显稳定的分子缓解期的CML患者停止TKI治疗时,大约一半病例中的这些细胞会重新开始生长,白血病进程得以恢复。因此,消除这些对TKI耐药的白血病干细胞是提高能够实现成功长期无治疗缓解(TFR)患者比例的关键步骤。因此,了解LSCs的生物学特性以及识别最终可使其与正常造血干细胞(HSCs)区分开来的表型和/或代谢差异,是设计以相当选择性的方式靶向LSCs同时保留正常对应细胞的策略的重要步骤。

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