Sontakke Pallavi, Jaques Jenny, Vellenga Edo, Schuringa Jan Jacob
Department of Experimental Hematology, Cancer Research Center Groningen, University Medical Center Groningen, University of Groningen, Groningen, Netherlands.
Stem Cells Int. 2016;2016:1625015. doi: 10.1155/2016/1625015. Epub 2016 Aug 25.
Over the past years, a wide variety of in vivo mouse models have been generated in order to unravel the molecular pathology of Chronic Myeloid Leukemia (CML) and to develop and improve therapeutic approaches. These models range from (conditional) transgenic models, knock-in models, and murine bone marrow retroviral transduction models followed by transplantation. With the advancement of immunodeficient xenograft models, it has become possible to use human stem/progenitor cells for in vivo studies as well as cells directly derived from CML patients. These models not only mimic CML but also have been instrumental in uncovering various fundamental mechanisms of CML disease progression and tyrosine kinase inhibitor (TKI) resistance. With the availability of iPSC technology, it has become feasible to derive, maintain, and expand CML subclones that are at least genetically identical to those in patients. The following review provides an overview of all murine as well as human xenograft models for CML established till date.
在过去几年中,为了阐明慢性髓性白血病(CML)的分子病理学,并开发和改进治疗方法,已经建立了各种各样的体内小鼠模型。这些模型包括(条件性)转基因模型、敲入模型以及小鼠骨髓逆转录病毒转导模型,随后进行移植。随着免疫缺陷异种移植模型的发展,使用人类干/祖细胞进行体内研究以及直接来源于CML患者的细胞成为可能。这些模型不仅模拟了CML,而且在揭示CML疾病进展和酪氨酸激酶抑制剂(TKI)耐药性的各种基本机制方面发挥了重要作用。随着诱导多能干细胞(iPSC)技术的出现,获得、维持和扩增至少在基因上与患者相同的CML亚克隆变得可行。以下综述概述了迄今为止建立的所有用于CML的小鼠和人类异种移植模型。