Activating FLT3 mutations in pediatric T-ALL. (A) Genomic PCR analysis for the FLT3 gene. PCR results for 6 pediatric T-ALL patient samples are shown. T-ALL patient 1179 shows a heterozygous FLT3/ITD mutation. No wild-type FLT3 is detected in T-ALL patient 2112, probably due to loss of heterozygosity of the wild-type allele. (B) Overview of the functional domains in the FLT3 tyrosine kinase receptor. Genomic position of the FLT3/ITD mutations detected in patients 1179 and 2112 are shown. Mutation position annotation is based on the FLT3 reference sequence NM_004119. (C) FLT3 mutation analysis of diagnosis and relapse material of T-ALL patient 1179. The FLT3/ITD mutation was present at diagnosis but absent at relapse. (D) Relative cKIT/CD117 mRNA expression indicated as percentage of GAPDH expression for the investigated pediatric T-ALL cohort (FLT3 wt vs FLT3 mut). For both groups the median FLT3 mRNA expression is shown. wt indicates wild type; mut, mutated; dx, at diagnosis; R, at relapse; and ^*, genomic position of the recently identified FLT3/ITD mutations in adult T-ALLs.²