: 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.
FLT3-targeted therapy restores GATA1 pathway function in NPM1/FLT3-ITD mutated acute myeloid leukaemia
Sorcini, D;Stella, A;Scialdone, A;Marra, A;De Falco, F;Adamo, F M;Dorillo, E;Geraci, C;Arcaleni, R;Rompietti, C;Esposito, A;Martelli, M P;Falini, B;Sportoletti, P
2023
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.File in questo prodotto:
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