Acute Myeloid Leukemia Research
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Redox regulation is defined as an actionable control point for extending differentiation-based therapies beyond genetically restricted AML subtypes and reinstates differentiation-associated transcriptional programs, suppresses leukemic stemness, and overcomes intrinsic differentiation resistance independently of APL-specific oncogenic drivers.
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Abstract Differentiation blockade is a defining hallmark of acute myeloid leukemia (AML). While all-trans retinoic acid (ATRA)-based differentiation therapy is curative in acute promyelocytic leukemia (APL), its efficacy in non-APL AML remains limited, and the determinants of differentiation responsiveness beyond APL are poorly understood. Here, we identify redox homeostasis reprogramming as a decisive and previously underappreciated regulator of differentiation therapy efficacy in AML and establish nanozyme-enabled redox modulation as a generalizable framework to restore differentiation competence. We rationally design a Fe–Se dual-atom nanozyme that reconstructs key catalytic features of natural glutathione peroxidase, enabling controlled and homeostatic regulation of intracellular oxidative stress. When combined with ATRA, this redox-guided strategy reinstates differentiation-associated transcriptional programs, suppresses leukemic stemness, and overcomes intrinsic differentiation resistance independently of APL-specific oncogenic drivers. Efficacy is demonstrated in human AML xenograft models and a hoxa9-driven differentiation-arrest zebrafish model. Collectively, this work defines redox regulation as an actionable control point for extending differentiation-based therapies beyond genetically restricted AML subtypes.
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@article{Wang2026Trans,
title = {All-Trans Retinoic Acid-Loaded Fe–N3–Se Single-Atom Nanozymes Enable Redox-Guided Differentiation Therapy for Acute Myeloid Leukemia},
author = {Wei Wang and Shuyu Wang and Shang Wang and Shuman Wang and Guoming Sun and Xiaowan Fan and Shibing Wang and Xiyun Yan and Peng Li and Kelong Fan and Xiangmin Tong},
journal = {ACS Nano},
year = {2026},
doi = {10.1021/acsnano.6c09298},
url = {https://doi.org/10.1021/acsnano.6c09298}
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