Inhibition of CRM1 reverses hypoxia-driven chemoresistance in acute myeloid leukemia via overcoming HIF-1α-mediated lysosomal sequestration
CRM1 inhibition by Selinexor re-establishes nuclear PHD2 residency, increases the degradation of HIF-1α in hypoxia, abrogates P-gp-mediated lysosomal anthracycline trapping, and confers potent <i>in-vitro</i> and <i>in-vivo</i> chemosensitization. These data provide mechanistic rationale for integrating Selinexor into salvage regimens for R/R-AML.
Authors
- Hancheng Qin (ORCID: https://orcid.org/0000-0003-0146-8206)
- Yuntian Ding
- Xiaobo Wang (ORCID: https://orcid.org/0000-0002-3311-1378)
- Xiaohui Feng (ORCID: https://orcid.org/0000-0003-0758-6609)
- Yu‐Ling Huang (ORCID: https://orcid.org/0000-0001-9914-1716)
- Yunxin Zeng
Institutions
- Sun Yat-sen University (CN)
- The Seventh Affiliated Hospital of Sun Yat-sen University (CN)
- First Affiliated Hospital of Guangzhou Medical University (CN)
- Guangzhou Blood Center (CN)
- Guangzhou First People's Hospital (CN)
- Guangzhou Medical University (CN)
Publication Details
- Journal
- Frontiers in Immunology
- Published
- 2025-11-27
- DOI
- https://doi.org/10.3389/fimmu.2025.1710230
- Primary Topic
- Cancer, Hypoxia, and Metabolism
- Type
- article
- Field-Weighted Citation Impact
- 0.00