A human ESC model for MLL-AF4 leukemic fusion gene reveals an impaired early hematopoietic-endothelial specification  

作　　者：Clara Bueno Rosa Montes Gustavo J Melen Verdnica Ramos-Mejia Pedro J Real Ver6nica Ayllo＇n Laura Sanchez Gertmdis Ligero Inmaculada Gutierrez-Aranda Agustin F Femfindez Mario F Fraga Inmaculada Moreno-Gimeno Deborah Btlrks Maria del Carmen Plaza-Calonge Juan C Rodriguez-Manzaneque Pablo Menendez 

机构地区：[1]GENyO （Pfizer-University of Granada-Andalusian Government Centre for Genomics and Oncological Research）, Avda de la Ilustraci6n 114, 18007 Granada, Spain [2]Cancer Epigenetics Laboratory, Instituto Universitario de Oncologia del Principado de Asturias, HUCA, Universidad de Oviedo, 33006 Oviedo, Spain [3]Department of Immunology and Oncology, Centro Nacional de Biotecnologia/CNB-CSIC, Cantoblanco, 28049 Madrid, Spain [4]Centro de Investigaci6n Principe Felipe, Valencia, Spain

出　　处：《Cell Research》2012年第6期986-1002,共17页细胞研究（英文版）

摘　　要：The MLL-AF4 fusion gene is a hallmark genomic aberration in high-risk acute iymphoblastic leukemia in infants. Although it is well established that MLL-AF4 arises prenatally during human development, its effects on hematopoietic development in utero remain unexplored. We have created a human-specific cellular system to study early hemato-endothelial development in MLL-AF4-expressing human embryonic stem cells （hESCs）. Functional studies, clonal analysis and gene expression profiling reveal that expression of MLL-AF4 in hESCs has a phenotypic, functional and gene expression impact. MLL-AF4 acts as a global transcriptional activator and a positive regulator of homeobox gene expression in hESCs. Functionally, MLL-AF4 enhances the specification of hemogenic precursors from hESCs

关 键 词：MLL-AF4 HESC HEMATOPOIESIS ENDOTHELIUM hemogenic precursors 

分 类 号：Q813[生物学—生物工程] Q78