Deletion of Q575 leads to targetable activation of FLT-3 in a patient with AML. (A) Circulating blasts as a percentage of total leukocytes in a patient with AML found to harbor a novel FLT-3/Q575Δ mutation. Timing of induction chemotherapy (7+3) and gilteritinib is indicated. (B) Expression of different FLT-3 mutations, including Q575Δ, in Ba/F3 cells leads to autophosphorylation of FLT-3 and downstream activation of signaling pathways, as detected by phospho-western analysis of whole-cell lysates. For wild-type FLT-3, cells were simulated with FLT-3 ligand before lysis. (C) Cells expressing FLT-3/Q575Δ were treated with increasing concentrations of the indicated FLT-3 TKIs, and total and phosphorylated FLT-3 was detected by western blot analysis. (D) Cells were cocultured in increasing concentrations of the indicated TKIs, and growth was measured by colorimetric MTT assay after 48 hours.