FLT3-ITD and FLT3-TKD show distinct associations with predefined STAT5 target gene subsets.

Analysis of STAT5 target genes in context of FLT3-ITD (A) and FLT3-TKD (B) mutation status in primary AML bone marrow samples. To avoid the interference of NPM1 mutations subgroups were composed, according to NPM1 mutation status. The differences in transcription factor target gene sets (STAT5A_01-04) result from different targeted motifs representing the broad spectrum of potential binding sites. FLT3-ITD was associated in all subgroups with significant enrichment of STAT5A_02 target genes and in no subgroup with enrichment of STAT5A_03 and STAT5A_04 target genes. FLT3-TKD showed a more diverse picture with enrichment of STAT5A_03 and STAT5A_04 target genes in some groups. In FLT3-TKD and NPM1-mutated patients no enrichment of STAT5 target genes could be detected. (+) indicates the presence of a mutation; (−) indicated the absence of a mutation; FDR: false discovery rate; p: nominal p-value (estimates the statistical significance of the enrichment score of the gene set); n.s.: not significant.