Blood: Glucoderosterone enhances the anti-FRT3 mutant AML activity of FRT3 inhibitors.

FLT3 is a gene with frequent mutations that is closely related to poor prognostication of acute myeloid leukemia (AML).
although most AML patients initially respond to FRT3 inhibitor treatment, they eventually relapse due to drug resistance.
, the mechanism by which FLT3 inhibitors are produced and the initial response to drugs that promote cell survival are unclear.
recent studies have shown that short-lived drug-sensitive cell subpopulars, known as drug-resistant persistents (DTP), can survive cytotoxic drug exposure even in the absence of drug-resistant mutations.
through RNA sequencing and drug screening, Gebru and others found that the treatment of FRT3-ITD AML cells with the selective FRT3 inhibitor quizartinib increased the inflammatory gene of DTPs, thereby enhancing their sensitivity to anti-inflammatory glucoscosteroids.
In the mechanism, the combined use of FLT3 inhibitors and glucosotrogens increases the degradation of proteases of apoptosis protein BIM and antioperative protein MCL-1 through glucosotrogen-dependent receptors, thereby enhancing cell death of FLT3 mutant cells without affecting the survival of wild cells.
addition, the researchers also confirmed increased anti-leukemia activity in the combined application of quezatini and desemitone in samples of primary AML patients and heteroglytic transplanted mice.
in summary, this study shows that the combined use of FLT3 inhibitors and glucoscosteroids has the potential to eliminate DTPs, thereby preventing small residual lesions, mutation resistance, and recurrence of FLT3 mutant AML.
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