Targeting RBPMS selectively eliminates FOXO1-mediated stem cell signatures in mouse models of acute myeloid leukemia
Ping Liu1,2, Sulin Zhang3, Bing-Yi Chen1
1Shanghai Institute of Nutrition and Health, University of Chinese Academy of Sciences, Chinese Academy of Sciences, Shanghai 200031, China.
Science Translational Medicine
|May 6, 2026
Summary
RNA binding protein with multiple splicing (RBPMS) is crucial for acute myeloid leukemia (AML) development. Inhibiting RBPMS halts leukemia growth with minimal impact on normal cells, identifying it as a potential therapeutic target.
Area of Science:
- Oncology
- Molecular Biology
- Hematology
Background:
- Leukemia presents a significant challenge due to high recurrence and poor patient outcomes.
- Identifying novel therapeutic targets crucial for leukemogenesis but sparing normal cells is essential.
Purpose of the Study:
- To investigate the role of RNA binding protein with multiple splicing (RBPMS) in acute myeloid leukemia (AML).
- To explore RBPMS as a potential therapeutic target for AML treatment.
Main Methods:
- Assessed RBPMS expression in AML and its correlation with prognosis.
- Investigated the effect of RBPMS inhibition on leukemia-initiating cells (LICs) and normal hematopoiesis.
- Elucidated the molecular mechanism involving m6A reader IGF2BP3 and FOXO1 mRNA stability.
- Utilized AML patient-derived xenograft (PDX) models to evaluate RBPMS inhibitor efficacy.
Main Results:
- RBPMS is highly expressed in AML and linked to poor prognosis.
- RBPMS inhibition suppressed LIC self-renewal and leukemia development without affecting normal hematopoiesis.
- RBPMS promotes FOXO1 mRNA stability and glycolysis in an m6A-dependent manner.
- A specific RBPMS inhibitor demonstrated therapeutic effects in AML PDX models.
Conclusions:
- RBPMS plays a critical role in leukemogenesis by regulating FOXO1 mRNA stability and glycolysis.
- Targeting RBPMS offers a promising therapeutic strategy for AML with minimal toxicity to normal hematopoietic cells.
