Loss of miR-31-5p drives hematopoietic stem cell malignant transformation and restoration eliminates leukemia stem cells in mice
Menée in vitro et à l'aide de modèles murins de leucémie myéloïde chronique, cette étude démontre que la perte de l'expression du microARN miR-31-5p favorise la transformation maligne des cellules souches hématopoïétiques et que la restauration de son expression élimine les cellules souches leucémiques
Leukemia stem cells (LSCs) originate from hematopoietic stem cells (HSCs), but our understanding of this transformation is limited. Here, Zhu and colleagues identified the microRNA miR-31-5p as a controller of the mode of energy metabolism in HSCs: Loss of miR-31-5p led to a transition away from glycolytic metabolism to oxidative phosphorylation, accumulation of the oncometabolite fumarate, and development of LSCs, whereas ectopic expression of miR-31-5p could eliminate LSCs. Treatment with encapsulated miR-31-5p and cytosine arabinoside inhibited progression of disease and improved survival in mice-bearing patient-derived acute myeloid leukemia, suggesting that miR-31-5p may hold promise as a treatment for leukemias in humans.