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DOI: Targeted Degradation of MYB as a Novel Therapeutic Strategy for Acute Myeloid Leukemias
Oleksandra Bondarenko , Boston, Massachusetts, USAAbstract
This study examines targeted degradation of the transcription factor MYB as a novel therapeutic avenue in acute myeloid leukemias. Its relevance stems from the limited efficacy of existing treatment regimens and the emergence of drug‐resistant disease forms. The work’s novelty lies in the integrated comparison of genetic models for MYB destabilization, chemical dTAG approaches, and the repurposing of low-molecular-weight compounds mebendazole and vitaferin A. Data are synthesized on MYB’s transformational properties critical for leukemic-clone maintenance, and experimental findings are reviewed on the suppression of transcriptional programs and induction of blast-cell death following complete factor elimination. Special attention is devoted to prospects for developing PROTAC degraders and molecular glues capable of catalyzing ubiquitin-dependent proteolysis of MYB at low compound doses. The research aims to construct a comprehensive assessment of the efficacy and safety of MYB-degradation strategies and to identify directions for further preclinical investigation. Methods include comparative analysis of peer-reviewed literature, critical appraisal of in vitro and in vivo data, and synthesis of pharmacodynamic profiles of the repurposed agents. The overall evaluation highlights the approach’s potential to overcome therapeutic resistance and improve patient survival. The findings will interest pharmacologists, oncologists, clinical researchers, and specialists in chemical biology.
Keywords
acute myeloid leukemia, MYB, proteasomal degradation, PROTAC
References
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