FLT3-targeted therapy restores GATA1 pathway function in NPM1/FLT3-ITD mutated acute myeloid leukaemia.
D SorciniA StellaA ScialdoneS SartoriA MarraR RossiF De FalcoF M AdamoE DorilloC GeraciR ArcaleniC RompiettiA EspositoL MorettiM G MameliM P MartelliBrunangelo FaliniPaolo SportolettiPublished in: EJHaem (2023)
One-third of newly diagnosed adult acute myeloid leukaemia (AML) carry FLT3 mutations, which frequently occur together with nucleophosmin ( NPM1 ) mutations and are associated with worse prognosis. FLT3 inhibitors are widely used in clinics with limitations due to drug resistance. AML cells carrying FLT3 mutations in both mouse models and patients present low expression of GATA1, a gene involved in haematopoietic changes preceding AML. Here, we show that FLT3 inhibition induces cellular responses and restores the GATA1 pathway and functions in NPM 1/ FLT3 -ITD mutated AML, thus providing a new mechanism of action for this drug.
Keyphrases
- acute myeloid leukemia
- newly diagnosed
- allogeneic hematopoietic stem cell transplantation
- transcription factor
- liver failure
- end stage renal disease
- chronic kidney disease
- primary care
- respiratory failure
- intensive care unit
- poor prognosis
- gene expression
- oxidative stress
- dendritic cells
- prognostic factors
- immune response
- bone marrow
- copy number
- aortic dissection
- extracorporeal membrane oxygenation
- peritoneal dialysis
- cell cycle arrest
- patient reported outcomes
- binding protein