Stubbs Matthew C, Krivtsov Andrei V
Incyte Corporation, Wilmington, Delaware.
Department of Pediatric Oncology, Dana-Farber Cancer Institute, Boston, Massachusetts.
Curr Protoc Pharmacol. 2017 Sep 11;78:14.42.1-14.42.19. doi: 10.1002/cpph.28.
MLL-rearranged leukemia represents approximately 5% to 10% of adult acute myelogenous leukemia (AML) and nearly half of all infant/pediatric acute leukemia cases. These leukemias have a poor prognosis, and there are no approved therapeutic options. The rearrangement in the MLL gene leads to aberrant expression of MLL-fusion proteins. These are transforming in murine bone marrow and, in particular, on stem cells and myeloid progenitors derived from bone marrow or fetal liver. The commonality of the MLL fusions is the in-frame fusion of 8 to 11 N-terminal exons of MLL1 (KMT2a) with the C-terminus of a partner fusion gene. Currently, over 80 different fusion partners are known. The protocols detailed in this unit focus on bone marrow-derived models only, using one particular MLL fusion, MLL-AF9. These models have proven effective for drug screening to predict clinical response. © 2017 by John Wiley & Sons, Inc.
MLL重排白血病约占成人急性髓性白血病（AML）的5%至10%，几乎占所有婴儿/儿童急性白血病病例的一半。这些白血病预后较差，且尚无获批的治疗方案。MLL基因重排导致MLL融合蛋白异常表达。这些蛋白在小鼠骨髓中具有转化能力，尤其是在源自骨髓或胎肝的干细胞和髓系祖细胞上。MLL融合的共同特点是MLL1（KMT2a）的8至11个N端外显子与一个伙伴融合基因的C端进行读码框内融合。目前，已知有80多种不同的融合伙伴。本单元详细介绍的方案仅聚焦于源自骨髓的模型，使用一种特定的MLL融合蛋白MLL-AF9。这些模型已被证明对药物筛选以预测临床反应有效。© 2017约翰威立国际出版公司
