Targeting fatty acid metabolism to abrogate differentiation block in pre-leukemia induced by AML1-ETO

To gain the underlying insight into the functional impact of AML1-ETO expressed in HSPCs, RNA-seq was performed on purified LT-HSCs and GMPs from the bone marrow (BM) of both AML1-ETO expressed (AML1/ETO) and Wild-Type (control) C57 mice. Our work suggested that AML1-ETO resulted in impaired hematopoietic reconstitution and increased self-renewal ability.The oxidative phosphorylation and glycolysis decreased significantly in AML1/ETO LT-HSCs accompanied by increased HSC quiescence and reduced cell cycling. Furthermore, it was observed that HSCs expressing AML1-ETO exhibited an increased requirement for fatty acids when they differentiated. Expression profiling by high throughput sequencing of LT-HSC cells and GMP cells for AML1/ETO mice and control mice