In paediatric AML, ~82% of patients with NUP98/NSD1 fusions also have FLT3/ITD, a known driver of treatment resistance. Patients with both genetic alterations had much lower rate of remission induction (27% vs 69% for FLT3/ITD patients with and without NUP98/NSD1, respectively) (Ostronoff et al. 2017). Although co-occurrence of these two events is associated with the low rate of response of patients to therapy, the mechanisms by which the co-expression of FLT3/ITD and NUP98/NSD1 induces innate treatment resistance is not well understood. We seek to understand such mechanisms, using RNA sequencing performed on 1,055 cases that were profiled as part of the AAML1031 clinical trial (Aplenc et al. 2016). We will infer transcription factor (TF) networks using regulatory network analysis and grouping co-expressed genes sharing common binding motifs of TFs, and attempt to comprehensively deduce the identity and consequences of dysregulated TF networks in treatment resistant paediatric AML.