See article, p. 125.

Although Ftl3 inhibitor (Flt3i)–targeting drugs offer clinical ben-efits in Flt3-mutant acute myeloid leukemia (AML), some patients are unresponsive (primary resistance) and others progress after initial response (secon-dary resistance). Alotaibi, Yilmaz, and colleagues characterize the genetic spectrum of resistance to type 1 and 2 Flt3i in primary and secondary cases. By targeted next-generation sequencing panel spanning over 20 genes commonly affected in AML, they compare the dynamics of genetic lesion occurrence and allele frequencies in baseline and relapse samples of 67 AML patients who progressed after achieving a complete response to a Flt3i in combination with chemotherapy. In 26% of the patients, the original Flt3 mutation was no longer detectable at relapse, whereas in the majority of the remaining cases, it persisted at near-pretreatment levels. Flt3-D835 mutation emerged in 30% of patients at relapse on type 2 Flt3i and correlated with 2-fold shorter overall survival (OS)....

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