IRF8
梅尔特克
生物
癌症研究
髓样
斑马鱼
造血
骨髓增生性肿瘤
髓系白血病
免疫学
转录因子
骨髓生成
细胞生物学
干细胞
骨髓
信号转导
遗传学
基因
受体酪氨酸激酶
骨髓纤维化
作者
Fangying Zhao,Yuqian Shi,Youkui Huang,Yandong Zhan,Lu Zhou,Y Li,Yang Wan,H Li,Hai Huang,Hua Ruan,Lingfei Luo,L Li
出处
期刊:Leukemia
[Springer Nature]
日期:2017-06-19
卷期号:32 (1): 149-158
被引量:21
摘要
Interferon regulatory factor (IRF)-8 is a critical transcription factor involved in the pathogenesis of myeloid neoplasia. However, the underlying mechanisms in vivo are not well known. Investigation of irf8-mutant zebrafish in this study indicated that Irf8 is evolutionarily conserved as an essential neoplastic suppressor through tight control of the proliferation and longevity of myeloid cells. Surviving irf8 mutants quickly developed a myeloproliferative neoplasm (MPN)-like disease with enhanced output of the myeloid precursors, which recurred after transplantation. Multiple molecules presented notable alteration and Mertk signaling was aberrantly activated in the hematopoietic cells in irf8 mutants. Transgenic mertk overexpression in Tg(coro1a:mertk) zebrafish recapitulated the myeloid neoplasia-like syndrome in irf8 mutants. Moreover, functional interference with Mertk, via morpholino knockdown or genetic disruption, attenuated the myeloid expansion phenotype caused by Irf8 deficiency. Therefore, Mertk signaling is a critical downstream player in the Irf8-mediated regulation of the progression of myeloid neoplasia. Our study extends the understanding of the mechanisms underlying leukemogenesis.
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