Pbx3-mediated suppression of type I interferon response contributes to leukemia progression driven by MLL-AF9

doi:10.1038/s41417-025-00888-7

	Pbx3-mediated suppression of type I interferon response contributes to leukemia progression driven by MLL-AF9
	Tang,Li1 ; Lu,Meng 1; Du,Yulong 1; Sun,Jianlong1,2
	2025-03-19
发表期刊	CANCER GENE THERAPY
ISSN	ISSN 1476-5500 (online) ISSN 0929-1903 (print)
EISSN	1476-5500
发表状态	已发表
DOI	10.1038/s41417-025-00888-7
摘要	Cell-intrinsic repression of inflammatory signaling supports the survival of acute myeloid leukemia blasts. However, how the cell-intrinsic inflammation status changes during AML progression remains elusive. Here, we used CRISPR-mediated genome editing to create a murine AML model driven by a chromosomal translocation between the mixed-lineage leukemia (Mll) gene and the Mllt3/Af9 gene. The resulting MLL-AF9 (MA9) fusion protein is sufficient to immortalize hematopoietic stem and progenitor cells (HSPCs) in vitro but insufficient to induce an overt leukemia phenotype in vivo rapidly. Leukemia progression in vivo is associated with a downregulation of type I interferon response genes, and this process depends on the upregulation of MA9 transcriptional target Pbx3 in the progenitor cell compartment. Accordingly, enhancing interferon response by interferon-alpha (IFN alpha) administration induces leukemic cell differentiation, and inhibiting MA9 transcriptional activity on top of the enhanced IFN signaling further delays leukemia progression. Our study underscores the importance of Pbx3-mediated suppression of interferon response genes in the progression of MA9-induced AML and highlights the potential application of type I interferon for its treatment.
URL	查看原文
收录类别	SCI
语种	英语
资助项目	HPC platform of ShanghaiTech University["2020YFA0710800","2021YFA0804700"] ; National Key R&D Program of China[81970102]
WOS研究方向	Biotechnology & Applied Microbiology ; Oncology ; Genetics & Heredity ; Research & Experimental Medicine
WOS类目	Biotechnology & Applied Microbiology ; Oncology ; Genetics & Heredity ; Medicine, Research & Experimental
WOS记录号	WOS:001447540600001
出版者	SPRINGERNATURE
文献类型	期刊论文
条目标识符	https://kms.shanghaitech.edu.cn/handle/2MSLDSTB/503642
专题	生命科学与技术学院_博士生生命科学与技术学院_PI研究组_孙建龙组
通讯作者	Sun,Jianlong
作者单位	1.School of Life Science and Technology, ShanghaiTech University 2.State Key Laboratory of Advanced Medical Materials and Devices, ShanghaiTech University
第一作者单位	生命科学与技术学院
通讯作者单位	生命科学与技术学院; 上海科技大学
第一作者的第一单位	生命科学与技术学院
推荐引用方式 GB/T 7714	Tang,Li,Lu,Meng,Du,Yulong,et al. Pbx3-mediated suppression of type I interferon response contributes to leukemia progression driven by MLL-AF9[J]. CANCER GENE THERAPY,2025.
APA	Tang,Li,Lu,Meng,Du,Yulong,&Sun,Jianlong.(2025).Pbx3-mediated suppression of type I interferon response contributes to leukemia progression driven by MLL-AF9.CANCER GENE THERAPY.
MLA	Tang,Li,et al."Pbx3-mediated suppression of type I interferon response contributes to leukemia progression driven by MLL-AF9".CANCER GENE THERAPY (2025).