Article
Activating JAK-mutations confer resistance to FLT3 kinase inhibitors in FLT3-ITD positive AML in vitro and in vivo.
Leukemia - 1 Jul 2021
Rummelt Christoph, Gorantla Sivahari P, Meggendorfer Manja, Charlet Anne, Endres Cornelia, Döhner Konstanze, Heidel Florian H, Fischer Thomas, Haferlach Torsten, Duyster Justus, von Bubnoff Nikolas
Abstract excerpt
An important limitation of FLT3 tyrosine kinase inhibitors (TKIs) in FLT3-ITD positive AML is the development of resistance. To better understand resistance to FLT3 inhibition, we examined FLT3-ITD positive cell lines which had acquired resistance to midostaurin or sorafenib. In 6 out of 23 TKI resistant cell lines we were able to detect a JAK1 V658F mutation, a mutation that led to reactivation of the...
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