IRF8
IRF4公司
干扰素调节因子
淋巴细胞生成
B细胞
生物
转录因子
癌症研究
免疫学
祖细胞
干细胞
细胞生物学
基因
遗传学
抗体
作者
Swee Heng Milon Pang,Martina Minnich,Pradnya Gangatirkar,Zhiqiang Zheng,Andreas D. Ebert,Guangchun Song,Ross A. Dickins,Lynn M. Corcoran,Charles G. Mullighan,Meinrad Busslinger,Nicholas D. Huntington,Stephen L. Nutt,Sebastian Carotta
出处
期刊:Leukemia
[Springer Nature]
日期:2016-03-02
卷期号:30 (6): 1375-1387
被引量:54
摘要
The Ets family transcription factor PU.1 and the interferon regulatory factor (IRF)4 and IRF8 regulate gene expression by binding to composite DNA sequences known as Ets/interferon consensus elements. Although all three factors are expressed from the onset of B-cell development, single deficiency of these factors in B-cell progenitors only mildly impacts on bone marrow B lymphopoiesis. Here we tested whether PU.1 cooperates with IRF factors in regulating early B-cell development. Lack of PU.1 and IRF4 resulted in a partial block in development the pre-B-cell stage. The combined deletion of PU.1 and IRF8 reduced recirculating B-cell numbers. Strikingly, all PU.1/IRF4 and ~50% of PU.1/IRF8 double deficient mice developed pre-B-cell acute lymphoblastic leukemia (B-ALL) associated with reduced expression of the established B-lineage tumor suppressor genes, Ikaros and Spi-B. These genes are directly regulated by PU.1/IRF4/IRF8, and restoration of Ikaros or Spi-B expression inhibited leukemic cell growth. In summary, we demonstrate that PU.1, IRF4 and IRF8 cooperate to regulate early B-cell development and to prevent pre-B-ALL formation.
科研通智能强力驱动
Strongly Powered by AbleSci AI