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急性髓系白血病研究中的新型单细胞技术。

Novel single-cell technologies in acute myeloid leukemia research.

作者信息

Gupta Soumyasri Das, Sachs Zohar

机构信息

Division of Hematology, Oncology, and Transplantation, Department Medicine, University of Minnesota, Minneapolis, Minn.

Division of Hematology, Oncology, and Transplantation, Department Medicine, University of Minnesota, Minneapolis, Minn; Masonic Cancer Center, University of Minnesota, Minneapolis, Minn.

出版信息

Transl Res. 2017 Nov;189:123-135. doi: 10.1016/j.trsl.2017.07.007. Epub 2017 Jul 25.

Abstract

Acute myeloid leukemia (AML) is a lethal malignancy because patients who initially respond to chemotherapy eventually relapse with treatment refractory disease. Relapse is caused by leukemia stem cells (LSCs) that reestablish the disease through self-renewal. Self-renewal is the ability of a stem cell to produce copies of itself and give rise to progeny cells. Therefore, therapeutic strategies eradicating LSCs are essential to prevent relapse and achieve long-term remission in AML. AML is a heterogeneous disease both at phenotypic and genotypic levels, and this heterogeneity extends to LSCs. Classical studies in AML have aimed at characterization of the bulk tumor population, thereby masking cellular heterogeneity. Single-cell approaches provide a novel opportunity to elucidate molecular mechanisms in heterogeneous diseases such as AML. In recent years, major advancements in single-cell measurement systems have revolutionized our understanding of the pathophysiology of AML and enabled the characterization of LSCs. Identifying the molecular mechanisms critical to AML LSCs will aid in the development of targeted therapeutic strategies to combat this deadly disease.

摘要

急性髓系白血病(AML)是一种致命的恶性肿瘤,因为最初对化疗有反应的患者最终会复发为难治性疾病。复发是由白血病干细胞(LSC)通过自我更新重新引发疾病所致。自我更新是干细胞产生自身拷贝并产生子代细胞的能力。因此,根除LSC的治疗策略对于预防AML复发并实现长期缓解至关重要。AML在表型和基因型水平上都是一种异质性疾病,这种异质性也延伸到LSC。AML的经典研究旨在表征肿瘤总体群体,从而掩盖了细胞异质性。单细胞方法为阐明诸如AML等异质性疾病中的分子机制提供了新机会。近年来,单细胞测量系统的重大进展彻底改变了我们对AML病理生理学的理解,并使LSC的表征成为可能。确定对AML-LSC至关重要的分子机制将有助于开发对抗这种致命疾病的靶向治疗策略。

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