Department of Clinical Medicine, Aarhus University, Aarhus, Denmark.
Department of Medicine, Huddinge, Karolinska Institute, Stockholm, Sweden.
Br J Haematol. 2019 Oct;187(2):144-156. doi: 10.1111/bjh.16104. Epub 2019 Aug 2.
The concept of leukaemic stem cells (LSCs) was experimentally suggested 25 years ago through seminal data from John Dick's group, who showed that a small fraction of cells from acute myeloid leukaemia (AML) patients were able to be adoptively transferred into immunodeficient mice. The initial estimation of the frequency was 1:250 000 leukaemic cells, clearly indicating the difficulties ahead in translating knowledge on LSCs to the clinical setting. However, the field has steadily grown in interest, expanse and importance, concomitantly with the realisation of the molecular background for AML culminating in the sequencing of hundreds of AML genomes. The literature is now ripe with contributions describing how different molecular aberrations are more or less specific for LSCs, as well as reports showing selectivity in targeting LSCs in comparison to normal haematopoietic stem and progenitor cells. However, we argue here that these important data have not yet been fully realised within the clinical setting. In this clinically focused review, we outline the difficulties in identifying and defining LSCs at the individual patient level, with special emphasis on intraclonal heterogeneity. In addition, we suggest areas of future focus in order to realise the concept as real-time benefit for AML patients.
25 年前，John Dick 研究团队的开创性数据提出了白血病干细胞（LSCs）的概念，他们表明，一小部分急性髓系白血病（AML）患者的细胞能够被过继转移到免疫缺陷小鼠中。最初估计频率为 1:250000 个白血病细胞，这清楚地表明，将 LSCs 的知识转化为临床环境具有很大的挑战性。然而，随着 AML 分子背景的认识不断深入，该领域的兴趣、规模和重要性稳步增长，最终导致数百个 AML 基因组的测序。现在，文献中充满了描述不同分子异常在多大程度上对 LSCs 具有特异性的贡献，以及与正常造血干细胞和祖细胞相比，靶向 LSCs 的选择性的报告。然而，我们在这里认为，这些重要数据在临床环境中尚未得到充分实现。在这篇以临床为重点的综述中，我们概述了在个体患者水平上识别和定义 LSCs 的困难，特别强调了克隆内异质性。此外，我们还提出了未来的关注领域，以实现 AML 患者的实时获益。
