Primary ALL blasts with high-level FLT3 expression, particularly those with MLL gene rearrangements, high hyperdiploidy, and FLT3 juxtamembrane domain mutations, are differentially sensitive to FLT3 inhibition. (A) MTT dose-response curves showing mean cytotoxic response to CEP-701 for infant and childhood ALL blasts, grouped by level of FLT3 expression, normalized to untreated controls. Error bars represent standard error of the mean (SEM). (B) Same data as in panel A but with the “FLT3 HIGH” group further stratified by cytogenetics. (C) Dot plot of individual samples' cytotoxic response (mean of triplicate wells) to CEP-701 at the 50-nM dose level, grouped by level of FLT3 expression and cytogenetics. All samples are FLT3 wild-type except where indicated. KD indicates FLT3 kinase domain mutation (ie, D835E substitution); ITD, FLT3 internal tandem duplication; JM del/ins, FLT3 juxtamembrane domain deletion/insertion. Error bars show mean ± SEM for each group. The dotted line indicates mean cytotoxic response of all 37 samples at 50 nM CEP-701 (59% untreated control). (D) Same data as in panel C, except with “FLT3 HIGH” samples only, grouped by FLT3 mutation status. WT indicates wild type; KD, kinase domain point mutation; JMD, juxtamembrane domain mutation; MUT, any mutation.