Ferrando Adolfo A, López-Otín Carlos
Department of Pediatrics, Columbia University, New York, New York, USA.
Department of Pathology and Cell Biology, Columbia University, New York, New York, USA.
Nat Med. 2017 Oct 6;23(10):1135-1145. doi: 10.1038/nm.4410.
Human leukemias are liquid malignancies characterized by diffuse infiltration of the bone marrow by transformed hematopoietic progenitors. The accessibility of tumor cells obtained from peripheral blood or through bone marrow aspirates, together with recent advances in cancer genomics and single-cell molecular analysis, have facilitated the study of clonal populations and their genetic and epigenetic evolution over time with unprecedented detail. The results of these analyses challenge the classic view of leukemia as a clonal homogeneous diffuse tumor and introduce a more complex and dynamic scenario. In this review, we present current concepts on the role of clonal evolution in lymphoid and myeloid leukemia as a driver of tumor initiation, disease progression and relapse. We also discuss the implications of these concepts in our understanding of the evolutionary mechanisms involved in leukemia transformation and therapy resistance.
人类白血病是一种液体恶性肿瘤,其特征是转化的造血祖细胞弥漫性浸润骨髓。从外周血或通过骨髓穿刺获得的肿瘤细胞的可及性,以及癌症基因组学和单细胞分子分析的最新进展,使得对克隆群体及其随时间的遗传和表观遗传进化的研究达到了前所未有的详细程度。这些分析结果挑战了白血病是克隆性均匀弥漫性肿瘤的经典观点,并引入了一个更复杂和动态的情况。在这篇综述中,我们阐述了关于克隆进化在淋巴样和髓样白血病中作为肿瘤起始、疾病进展和复发驱动因素的作用的当前概念。我们还讨论了这些概念对我们理解白血病转化和治疗耐药所涉及的进化机制的影响。