Blood: Glucocorticoids enhance anti-FLT3 mutation AML activity in FLT3 inhibitors

FLT3 is a gene with frequent mutations that are closely related to poor prognosis of acute myeloid leukemia (AML)Although most AML patients initially respond to FLT3 inhibitor therapy, they eventually relapse due to drug resistanceAt present, the mechanism of resistance to the production of FLT3 inhibitors and the initial response to drugs that promote cell survival are unclearrecent studieshave shown that the short-lived drug-sensitive cell subgroup, known as drug-resistant persistents (DTP), can survive from cytotoxic drug exposure even in the absence of drug-resistant mutationsThrough RNA sequencing and drug screening, Gebru et alfound that the treatment of FLT3-ITD AML cells with selective FLT3 inhibitor kezzanine (quizartinib) increased the inflammatory gene of DTPs, thereby increasing their sensitivity to anti-inflammatory corticosteroidsin the mechanism, FLT3 inhibitors and glucocorticoids were used in combination with glucocorticoid-dependent receptors to increase protease degradation of apoptosis protein BIM and antiapopitis protein MCL-1, thereby enhancing cell death of FLT3 mutant cells and not affecting the survival of wild cellsIn addition, the researchers confirmed an increase in anti-leukemia activity during the combination of Quezatinib and dexamethasone in primary AML patient samples and xenotransplanted mouse modelsin general,, this study shows that the combination of FLT3 inhibitors and glucocorticoids has the potential to eliminate DTPs, thus preventing the micro-residual lesions, mutation resistance and recurrence of FLT3-mutant AML