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World J Stem Cells. Jul 26, 2026; 18(7): 119893
Published online Jul 26, 2026. doi: 10.4252/wjsc.119893
Published online Jul 26, 2026. doi: 10.4252/wjsc.119893
Bone marrow niche adaptation, leukemic stem cell persistence, and therapeutic resistance in FLT3-mutated leukemia
Huai-Bin Zhang, Hui-Hui Jiang, Jian-Chuan Deng, Nan Zhang, Department of Hematology, The Second Affiliated Hospital of Chongqing Medical University, Chongqing 400010, China
Co-first authors: Huai-Bin Zhang and Hui-Hui Jiang.
Co-corresponding authors: Jian-Chuan Deng and Nan Zhang.
Author contributions: Zhang HB and Jiang HH contributed equally to this manuscript and are co-first authors of this manuscript. Zhang HB collected and reviewed the literature and drafted the manuscript; Jiang HH assisted with literature collection and manuscript revision; Deng JC and Zhang N contributed equally as co-corresponding authors. Deng JC conceptualized the study and revised the manuscript; Zhang N designed the study and supervised the manuscript preparation. All authors read and approved the final version of the manuscript.
AI contribution statement: No AI tools were used for literature retrieval, data interpretation, or scientific content generation in this manuscript.
Supported by the National Natural Science Foundation of China, No. 82500204; and the Natural Science Foundation of Chongqing, No. CSTB2025NSCQ-GPX1181.
Conflict-of-interest statement: All the authors report no relevant conflicts of interest for this article.
Corresponding author: Nan Zhang, Department of Hematology, The Second Affiliated Hospital of Chongqing Medical University, No. 288 Tianwen Avenue, Nan’an District, Chongqing 400010, China. zhangnan@hospital.cqmu.edu.cn
Received: February 10, 2026
Revised: March 9, 2026
Accepted: June 9, 2026
Published online: July 26, 2026
Processing time: 165 Days and 4.2 Hours
Revised: March 9, 2026
Accepted: June 9, 2026
Published online: July 26, 2026
Processing time: 165 Days and 4.2 Hours
Core Tip
Core Tip: FLT3-mutated leukemia remains clinically challenging because therapeutic resistance is driven not only by intrinsic oncogenic signaling, but also by adaptive interactions with the bone marrow microenvironment. This review highlights how stromal protection, chemokine-mediated retention, hypoxic support, metabolic rewiring, immune evasion, and leukemia stem cell persistence collectively promote treatment failure and relapse. It also summarizes current and emerging therapeutic strategies aimed at cotargeting FLT3 signaling, the supportive niche, and stem cell-related vulnerabilities.