急性髓系白血病中对白血病干细胞的治疗靶向
Therapeutic targeting of leukemia stem cells in acute myeloid leukemia.
发表日期:2023
作者:
Karina Barbosa, Aniruddha J Deshpande
来源:
Stem Cell Research & Therapy
摘要:
造血干细胞的一个显著特点是其自我更新能力。由于自我更新对于持续补充造血干细胞库是非常重要的,所以这个特性经常在血液癌症中被利用。急性髓系白血病(AML)被认为是一种等级行列,其中自我更新的白血病干细胞(LSCs)产生大部分肿瘤。关于LSCs的最早的特征研究是通过评估前瞻性分离的AML干细胞候选者的能力来使小鼠内的整个肿瘤重新复制。进一步的研究表明,LSCs可能负责化疗抵抗,因此作为继发疾病和白血病复发的储备库。近年来,许多研究帮助揭示了骨髓病理学(包括白血病)中克隆性的复杂性。已经确定了许多区分LSC和正常造血干细胞的特征,并且这些研究为针对AML LSCs开辟了多种途径,对AML患者的临床管理产生了影响。本综述将讨论AML中自我更新的作用及其影响,分辨正常干细胞和白血病干细胞之间的特点,以及针对AML LSCs的治疗靶点的机会。版权所有©2023 Barbosa和Deshpande。
One of the distinguishing properties of hematopoietic stem cells is their ability to self-renew. Since self-renewal is important for the continuous replenishment of the hematopoietic stem cell pool, this property is often hijacked in blood cancers. Acute myeloid leukemia (AML) is believed to be arranged in a hierarchy, with self-renewing leukemia stem cells (LSCs) giving rise to the bulk tumor. Some of the earliest characterizations of LSCs were made in seminal studies that assessed the ability of prospectively isolated candidate AML stem cells to repopulate the entire heterogeneity of the tumor in mice. Further studies indicated that LSCs may be responsible for chemotherapy resistance and therefore act as a reservoir for secondary disease and leukemia relapse. In recent years, a number of studies have helped illuminate the complexity of clonality in bone marrow pathologies, including leukemias. Many features distinguishing LSCs from normal hematopoietic stem cells have been identified, and these studies have opened up diverse avenues for targeting LSCs, with an impact on the clinical management of AML patients. This review will discuss the role of self-renewal in AML and its implications, distinguishing characteristics between normal and leukemia stem cells, and opportunities for therapeutic targeting of AML LSCs.Copyright © 2023 Barbosa and Deshpande.