eJHaem (Nov 2023)
FLT3‐targeted therapy restores GATA1 pathway function in NPM1/FLT3‐ITD mutated acute myeloid leukaemia
- D Sorcini,
- A Stella,
- A Scialdone,
- S Sartori,
- A Marra,
- R Rossi,
- F De Falco,
- FM Adamo,
- E Dorillo,
- C Geraci,
- R Arcaleni,
- C Rompietti,
- A Esposito,
- L Moretti,
- MG Mameli,
- MP Martelli,
- B Falini,
- P Sportoletti
Affiliations
- D Sorcini
- Department of Medicine and Surgery Centro di Ricerca Emato‐Oncologiche University of Perugia PerugiaItaly
- A Stella
- Department of Medicine and Surgery Centro di Ricerca Emato‐Oncologiche University of Perugia PerugiaItaly
- A Scialdone
- Department of Medicine and Surgery Centro di Ricerca Emato‐Oncologiche University of Perugia PerugiaItaly
- S Sartori
- Department of Medicine and Surgery Centro di Ricerca Emato‐Oncologiche University of Perugia PerugiaItaly
- A Marra
- Department of Medicine and Surgery Centro di Ricerca Emato‐Oncologiche University of Perugia PerugiaItaly
- R Rossi
- Department of Medicine and Surgery Centro di Ricerca Emato‐Oncologiche University of Perugia PerugiaItaly
- F De Falco
- Department of Medicine and Surgery Centro di Ricerca Emato‐Oncologiche University of Perugia PerugiaItaly
- FM Adamo
- Department of Medicine and Surgery Centro di Ricerca Emato‐Oncologiche University of Perugia PerugiaItaly
- E Dorillo
- Department of Medicine and Surgery Centro di Ricerca Emato‐Oncologiche University of Perugia PerugiaItaly
- C Geraci
- Department of Medicine and Surgery Centro di Ricerca Emato‐Oncologiche University of Perugia PerugiaItaly
- R Arcaleni
- Department of Medicine and Surgery Centro di Ricerca Emato‐Oncologiche University of Perugia PerugiaItaly
- C Rompietti
- Department of Medicine and Surgery Centro di Ricerca Emato‐Oncologiche University of Perugia PerugiaItaly
- A Esposito
- Department of Medicine and Surgery Centro di Ricerca Emato‐Oncologiche University of Perugia PerugiaItaly
- L Moretti
- Department of Medicine and Surgery Centro di Ricerca Emato‐Oncologiche University of Perugia PerugiaItaly
- MG Mameli
- Department of Medicine and Surgery Centro di Ricerca Emato‐Oncologiche University of Perugia PerugiaItaly
- MP Martelli
- Department of Medicine and Surgery Centro di Ricerca Emato‐Oncologiche University of Perugia PerugiaItaly
- B Falini
- Department of Medicine and Surgery Centro di Ricerca Emato‐Oncologiche University of Perugia PerugiaItaly
- P Sportoletti
- Department of Medicine and Surgery Centro di Ricerca Emato‐Oncologiche University of Perugia PerugiaItaly
- DOI
- https://doi.org/10.1002/jha2.738
- Journal volume & issue
-
Vol. 4,
no. 4
pp. 1100 – 1104
Abstract
Abstract 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 NPM1/FLT3‐ITD mutated AML, thus providing a new mechanism of action for this drug.
Keywords
- acute myeloid leukaemia
- FLT3 inhibitors
- FLT3‐ITD
- GATA1
- heamatological malignancies
- leukaemia therapy
