Rora Regulates Hematopoietic Stem Cell Phenotypes and Progression of Chronic Myelogenous Leukemia

Ning Li; Yunyu Feng; Nan Wang; Wei He; Hongjian Li; Xue Cui; Bochuan Wang; Runkuan Qin; Huandi Qiu; Qiang Qiu; Li Zheng; Yuanyuan Sun; Linye He; Cong Pan; Anping Su; Zhihui Li; Yiguo Hu

doi:10.1016/j.ajpath.2025.12.010

Rora Regulates Hematopoietic Stem Cell Phenotypes and Progression of Chronic Myelogenous Leukemia

Am J Pathol. 2026 Jan 15:S0002-9440(26)00004-0. doi: 10.1016/j.ajpath.2025.12.010. Online ahead of print.

Authors

Ning Li¹, Yunyu Feng¹, Nan Wang¹, Wei He², Hongjian Li³, Xue Cui¹, Bochuan Wang¹, Runkuan Qin¹, Huandi Qiu², Qiang Qiu⁴, Li Zheng⁵, Yuanyuan Sun², Linye He⁶, Cong Pan⁷, Anping Su⁶, Zhihui Li⁶, Yiguo Hu⁸

Affiliations

¹ State Key Laboratory of Biotherapy, West China Hospital, Sichuan University, Chengdu, China.
² State Key Laboratory of Biotherapy, West China Hospital, Sichuan University, Chengdu, China; Department of Clinical Translational Innovation Center and Molecular Medicine Research Center, Chengdu, China.
³ Institute for Immunology and School of Medicine, Tsinghua University, Beijing, China.
⁴ Department of Hematology and Research Laboratory of Hematology, State Key Laboratory of Biotherapy, West China Hospital, Sichuan University, Chengdu, China.
⁵ State Key Laboratory of Biotherapy, West China Hospital, Sichuan University, Chengdu, China; Institute of Cardiovascular Surgery, West China Hospital, Sichuan University, Chengdu, China.
⁶ Laboratory of Thyroid and Parathyroid Disease, Frontiers Science Center for Disease-Related Molecular Network, West China Hospital, Sichuan University, Chengdu, China; Department of Thyroid Surgery, West China Hospital, Sichuan University, Chengdu.
⁷ School of Biological Sciences, Guizhou Education University, Guiyang; Translational Medicine Research Center, eBond Pharmaceutical Technology Co, Ltd, Chengdu, China.
⁸ State Key Laboratory of Biotherapy, West China Hospital, Sichuan University, Chengdu, China; Department of Thyroid Surgery, West China Hospital, Sichuan University, Chengdu. Electronic address: huyiguo@scu.edu.cn.

PMID: 41547479
DOI: 10.1016/j.ajpath.2025.12.010

Abstract

Hematopoietic stem cell (HSC) aging leads to hematological dysfunction and diseases, but the regulatory factors involved remain incompletely characterized. In this study, the HSC Aging-Associated TFs Catalog System model was developed to identify transcription factors (TFs) that resist HSC aging. This approach revealed RORA as a key aging-negative-associated TF. Rora deletion in HSCs caused aged phenomes and functionally impaired their reconstitutive capacity. Additionally, Rora deficiency impaired leukemia stem cell proliferation and prevented chronic myelogenous leukemia. These findings establish RORA as a critical regulator in maintaining HSC function and provide insights into its therapeutic potential in hematological disorders.