Wellcome-MRC Cambridge Stem Cell Institute, Jeffrey Cheah Biomedical Centre, Department of Haematology, University of Cambridge, Cambridge CB2 0AW, United Kingdom.
Haematological Cancer Genetics, Wellcome Trust Sanger Institute, Cambridge CB10 1SA, United Kingdom.
Cold Spring Harb Perspect Med. 2021 Jan 4;11(1):a035535. doi: 10.1101/cshperspect.a035535.
Mouse models of human myeloid malignancies support the detailed and focused investigation of selected driver mutations and represent powerful tools in the study of these diseases. Carefully developed murine models can closely recapitulate human myeloid malignancies in vivo, enabling the interrogation of a number of aspects of these diseases including their preclinical course, interactions with the microenvironment, effects of pharmacological agents, and the role of non-cell-autonomous factors, as well as the synergy between co-occurring mutations. Importantly, advances in gene-editing technologies, particularly CRISPR-Cas9, have opened new avenues for the development and study of genetically modified mice and also enable the direct modification of mouse and human hematopoietic cells. In this review we provide a concise overview of some of the important mouse models that have advanced our understanding of myeloid leukemogenesis with an emphasis on models relevant to clonal hematopoiesis, myelodysplastic syndromes, and acute myeloid leukemia with a normal karyotype.
人类髓系恶性肿瘤的小鼠模型支持对选定驱动突变的详细和集中研究，是研究这些疾病的有力工具。精心开发的鼠模型可以在体内非常准确地重现人类髓系恶性肿瘤，从而可以研究这些疾病的许多方面，包括它们的临床前过程、与微环境的相互作用、药理作用、非细胞自主因素的作用，以及共存突变之间的协同作用。重要的是，基因编辑技术的进步，特别是 CRISPR-Cas9，为基因修饰小鼠的开发和研究开辟了新的途径，也使直接修饰小鼠和人类造血细胞成为可能。在这篇综述中，我们简要概述了一些重要的小鼠模型，这些模型加深了我们对髓系白血病发生的理解，重点介绍了与克隆性造血、骨髓增生异常综合征和正常核型急性髓系白血病相关的模型。
