Kinomics, proteomics, and signaling dynamics for novel combination therapies in MLL-rearranged AML

(A) Overall study design for novel combination therapies (B) Constructed kinome trees showing the overall kinase derived peptide activity in 15 individual primary MLL-rearranged AML samples versus 5 NBM samples to identify the distribution and the overlap of kinase activity. Combined kinome trees revealed induced JNK annotated peptide activity in MLL-rearranged AML. (C) Representative protein kinase phosphorylation arrays of primary MLL-rearranged AML (n=9 in total) versus NBM (n=4 in total). Phosphoproteomic analysis identified induced phosphorylation levels of MEK and CREB protein kinases in MLL-rearranged AML. (D) Evaluation of AML cell survival of an anticipated successful combined therapeutic strategy in MLL-rearranged AML, showing the synergistic beneficial effect of combined MEK and VEGFR-2 inhibition in MLL-rearranged AML cell line THP-1.