| GeneLibs

题目:: LEF-1 is crucial for neutrophil granulocytopoiesis and its expression is severely reduced in congenital neutropenia.
作者:: Skokowa(Julia),Cario(Gunnar),Uenalan(Murat),Schambach(Axel),Germeshausen(Manuela),Battmer(Karin),Zeidler(Cornelia),Lehmann(Ulrich),Eder(Matthias),Baum(Christopher),Grosschedl(Rudolf),Stanulla(Martin),Scherr(Michaela),Welte(Karl)
状态:: 发布时间2006-10-25 , 更新时间 2012-11-15
期刊:: Nat Med
摘要:: We demonstrate here that lymphoid enhancer-binding factor 1 (LEF-1) mediates the proliferation, survival and differentiation of granulocyte progenitor cells. We initially documented the importance of this transcription factor in the bone marrow of individuals with severe congenital neutropenia (CN) with a 'differentiation block' at the promyelocytic stage of myelopoiesis. LEF-1 expression was greatly reduced or even absent in CN arrested promyelocytes, resulting in defective expression of the LEF-1 target genes CCND1, MYC and BIRC5, encoding cyclin D1 (ref. 2), c-Myc and survivin, respectively. In contrast, healthy individuals showed highest LEF-1 expression in promyelocytes. Reconstitution of LEF-1 in early hematopoietic progenitors of two individuals with CN corrected the defective myelopoiesis and resulted in the differentiation of these progenitors into mature granulocytes. Repression of endogenous LEF-1 by specific short hairpin RNA inhibited proliferation and induced apoptosis of CD34(+) progenitors from healthy individuals and of cells from two myeloid lines (HL-60 and K562). C/EBPalpha, a key transcription factor in granulopoiesis, was directly regulated by LEF-1. These observations indicate that LEF-1 is an instructive factor regulating neutrophilic granulopoiesis whose absence plays a critical role in the defective maturation program of myeloid progenitors in individuals with CN.
语言:: eng
DOI:: 10.1038/nm1474

文献库文献相关信息

DataTable pData

联系方式

微信公众号

文献库 文献相关信息

DataTable pData

联系方式

微信公众号

文献库文献相关信息