Association of mutations with all drugs Sorafenib+NPM1:FLT3_ITD KW−2449+FLT3_ITD 12 Sunitinib+NPM1:FLT3_ITD Crenolanib+FLT3_ITD Sorafenib+FLT3_ITD 8 Patients 20 40 Pazopanib (GW786034)+NRAS 60 80 log10 overall FDR log10 overall − Vemurafenib (PLX−4032)+NRAS 4 Tivozanib (AV−951)+NRAS Crizotinib (PF−2341066)+KRAS NVP−TAE684+KRAS 0 −100 −50 0 50 100 Average Difference Association of mutations with 17−AAG (Tanespimycin) FLT3_ITD 6 NPM1:FLT3_ITD 4 Patients 20 40 TP53 log10 FDR 60 − FLT3_ITD:DNMT3A NPM1:FLT3_ITD:DNMT3A NPM1 2 FLT3_ITD:TET2 FLT3_ITD:ASXL1 NPM1:FLT3_ITD:TET2 FLT3_ITD:WT1 TP53:NRAS FLT3_ITD:IDH2 NPM1:DNMT3A FLT3_ITD:RUNX1 0 −50 −25 0 25 50 Average Difference Association of mutations with A−674563 NPM1:FLT3_ITD FLT3_ITD 4 3 Patients 20 40 2 FLT3_ITD:TET2 60 log10 FDR − 80 NPM1:FLT3_ITD:DNMT3A NPM1 FLT3_ITD:DNMT3A FLT3_ITD:IDH2 NPM1:IDH2 CREBBP 1 NPM1:FLT3_ITD:TET2 FLT3_ITD:WT1 0 −60 −30 0 30 60 Average Difference Association of mutations with ABT−737 1.00 0.75 Patients 10 20 0.50 30 log10 FDR 40 − 50 0.25 0.00 −50 −25 0 25 Average Difference Association of mutations with AT7519 1.00 0.75 Patients 20 0.50 40 log10 FDR 60 − 0.25 0.00 −25 0 25 Average Difference Association of mutations with AZD1480 FLT3_ITD 3 NPM1:FLT3_ITD NPM1:SRSF2:IDH2 2 Patients 20 40 60 log10 FDR − NPM1:SRSF2 FLT3_ITD:TET2 80 1 FLT3_ITD:IDH2 0 −60 −40 −20 0 20 Average Difference Association of mutations with Afatinib (BIBW−2992) 1.00 0.75 Patients 20 0.50 40 60 log10 FDR − 80 0.25 0.00 −20 0 20 40 Average Difference Association of mutations with Alisertib (MLN8237) NPM1:FLT3_ITD 1.2 NPM1:FLT3_ITD:TET2 0.8 Patients 20 40 60 log10 FDR − 80 0.4 0.0 −40 −20 0 20 Average Difference Association of mutations with Axitinib (AG−013736) 2.5 FLT3_ITD NPM1:FLT3_ITD 2.0 NPM1:FLT3_ITD:DNMT3A FLT3_ITD:DNMT3A NPM1 NPM1:DNMT3A 1.5 TP53:NRAS Patients 20 FLT3_ITD:IDH2 40 60 log10 FDR − 80 1.0 0.5 0.0 −30 0 30 60 Average Difference Association of mutations with BEZ235 RUNX1 1.00 0.75 Patients 20 0.50 40 log10 FDR 60 − 0.25 0.00 −75 −50 −25 0 25 Average Difference Association of mutations with BI−2536 1.00 0.75 Patients 5 10 0.50 15 log10 FDR − 20 0.25 0.00 −30 −20 −10 0 10 20 Average Difference Association of mutations with BMS−345541 2.0 PDS5B 1.5 Patients 20 1.0 40 60 log10 FDR − 80 0.5 0.0 −40 −20 0 20 Average Difference Association of mutations with Barasertib (AZD1152−HQPA) FLT3_ITD:IDH2 NPM1:FLT3_ITD FLT3_ITD 7.5 Patients 5.0 20 40 log10 FDR 60 − NPM1 NPM1:FLT3_ITD:TET2 FLT3_ITD:WT1 FLT3_ITD:TET2 2.5 FLT3_ITD:ASXL1 NPM1:IDH1 FLT3_ITD:DNMT3A PTPN11 NPM1:IDH2 NPM1:FLT3_ITD:DNMT3A ASXL1:SRSF2 NPM1:SRSF2 KRAS STAG2:SRSF2 0.0 −100 −50 0 50 Average Difference Association of mutations with Bay 11−7085 FLT3_ITD FLT3_ITD:IDH2 NPM1:FLT3_ITD 1.5 NPM1:IDH2 SMC1A NPM1 Patients 10 1.0 NPM1:FLT3_ITD:DNMT3A 20 30 log10 FDR 40 − 50 0.5 0.0 −60 −40 −20 0 20 40 Average Difference Association of mutations with Bortezomib (Velcade) 1.00 0.75 Patients 20 0.50 40 60 log10 FDR − 80 0.25 0.00 −25 0 25 50 Average Difference Association of mutations with Bosutinib (SKI−606) FLT3_ITD 4 Patients 20 40 60 log10 FDR − FLT3_ITD:RUNX1 KRAS 80 NPM1:FLT3_ITD 2 FLT3_ITD:IDH2 FLT3_ITD:DNMT3A FLT3_ITD:TET2 NPM1:FLT3_ITD:DNMT3A 0 −60 −30 0 30 Average Difference Association of mutations with CHIR−99021 1.00 0.75 Patients 20 0.50 40 60 log10 FDR − 80 0.25 0.00 −40 −20 0 20 Average Difference Association of mutations with CI−1040 (PD184352) NRAS 3 Patients 2 20 NPM1:NRAS 40 60 log10 FDR − 80 NPM1:DNMT3A:NRAS 1 DNMT3A:NRAS 0 −50 −25 0 25 Average Difference Association of mutations with CYT387 FLT3_ITD NRAS NPM1:FLT3_ITD 2 SRSF2:NRAS Patients FLT3_ITD:DNMT3A 20 40 60 log10 FDR IDH1 − 80 1 0 −30 0 30 60 Average Difference Association of mutations with Cabozantinib FLT3_ITD NPM1:FLT3_ITD 10 FLT3_ITD:DNMT3A Patients NPM1:FLT3_ITD:DNMT3A 20 40 log10 FDR NPM1 60 − FLT3_ITD:IDH2 5 NPM1:FLT3_ITD:TET2 NPM1:DNMT3A TP53 FLT3_ITD:TET2 NPM1:TET2 NRAS TP53:NRAS KRAS NPM1:SRSF2 NPM1:IDH2 FLT3_ITD:RUNX1 FLT3_ITD:WT1 ASXL1 NPM1:FLT3 ASXL1:KRAS FLT3_ITD:TET2:DNMT3A DNMT3A ASXL1:SRSF2 STAG2:ASXL1 0 NPM1:TET2:DNMT3A FLT3_ITD:FLT3 −100 −50 0 50 100 Average Difference Association of mutations with Canertinib (CI−1033) FLT3_ITD:IDH2 2.0 FLT3_ITD NPM1:FLT3_ITD 1.5 FLT3_ITD:TET2 Patients SMC1A 20 1.0 40 log10 FDR 60 − 0.5 0.0 −60 −40 −20 0 20 Average Difference Association of mutations with Cediranib (AZD2171) RUNX1 FLT3_ITD:RUNX1 U2AF1 1.0 Patients 20 40 log10 FDR 60 − 0.5 0.0 −50 −25 0 25 Average Difference Association of mutations with Crenolanib FLT3_ITD NPM1:FLT3_ITD 10 Patients FLT3_ITD:DNMT3A 20 FLT3_ITD:FLT3 40 log10 FDR NPM1:FLT3_ITD:DNMT3A 60 − NPM1:FLT3_ITD:FLT3 5 NPM1:FLT3_ITD:TET2 NPM1 FLT3_ITD:TET2 NPM1:DNMT3A FLT3_ITD:SF3B1 KRAS FLT3_ITD:RUNX1 TP53 FLT3_ITD:WT1 ASXL1:KRAS NPM1:FLT3 SRSF2 NPM1:DNMT3A:FLT3 FLT3 NRAS SRSF2:NRAS DNMT3A:FLT3 0 CBFB.MYH11 −100 −50 0 50 Average Difference Association of mutations with Crizotinib (PF−2341066) KRAS 3 TP53:NRAS NRAS FLT3_ITD 2 Patients NPM1:FLT3_ITD 20 FLT3_ITD:SRSF2 40 60 log10 FDR − BCOR IDH2 80 SMC1A 1 NPM1:CEBPA 0 −30 0 30 60 Average Difference Association of mutations with DBZ NPM1:IDH2 4 3 Patients 20 2 40 log10 FDR 60 − FLT3_ITD:IDH2 FLT3_ITD NPM1:SRSF2:IDH2 IDH2 1 FLT3_ITD:IDH1 NPM1 ASXL1 0 −60 −40 −20 0 20 40 Average Difference Association of mutations with Dasatinib 1.5 PML.RARA TP53:NRAS TP53 1.0 KRAS Patients 20 40 60 log10 FDR − 80 0.5 0.0 −50 0 50 Average Difference Association of mutations with Doramapimod (BIRB 796) 1.00 0.75 Patients 20 0.50 40 60 log10 FDR − 80 0.25 0.00 −30 0 30 60 Average Difference Association of mutations with Dovitinib (CHIR−258) FLT3_ITD 12 NPM1:FLT3_ITD 8 Patients 20 FLT3_ITD:DNMT3A 40 log10 FDR 60 − NPM1:FLT3_ITD:DNMT3A FLT3_ITD:IDH2 4 NPM1 TP53 NPM1:FLT3_ITD:TET2 FLT3_ITD:TET2 NRAS TP53:NRAS FLT3_ITD:FLT3 NPM1:DNMT3A KRAS NPM1:IDH1 FLT3_ITD:RUNX1 FLT3_ITD:WT1 0 −50 0 50 Average Difference Association of mutations with Elesclomol PML.RARA 2.0 1.5 Patients 20 40 log10 FDR 1.0 60 − 0.5 0.0 0 50 100 Average Difference Association of mutations with Entospletinib (GS−9973) NPM1:FLT3_ITD 4 FLT3_ITD NPM1 3 NPM1:FLT3_ITD:DNMT3A Patients 10 NPM1:DNMT3A 20 2 FLT3_ITD:DNMT3A 30 log10 FDR FLT3_ITD:IDH2 40 − NPM1:IDH2 50 NPM1:TET2:DNMT3A FLT3_ITD:IDH1 STAG2 IDH2 1 NPM1:IDH1 NPM1:FLT3 DNMT3A NRAS DNMT3A:IDH2 0 −40 −20 0 20 40 Average Difference Association of mutations with Entrectinib 1.0 0.8 Patients 5 0.6 10 15 log10 FDR − 20 0.4 0.2 −40 −20 0 20 Average Difference Association of mutations with Erlotinib 8 FLT3_ITD 6 NPM1:FLT3_ITD Patients 20 4 40 60 log10 FDR − 80 NPM1:FLT3_ITD:DNMT3A NPM1 NPM1:FLT3_ITD:TET2 NRAS 2 FLT3_ITD:DNMT3A FLT3_ITD:TET2 KRAS NPM1:IDH2 NPM1:IDH1 STAG2:ASXL1 FLT3_ITD:IDH2 0 −40 −20 0 20 Average Difference Association of mutations with Flavopiridol 1.2 NRAS 0.9 Patients 20 0.6 40 log10 FDR 60 − 0.3 0.0 −50 −25 0 25 50 Average Difference Association of mutations with Foretinib (XL880) FLT3_ITD NPM1:FLT3_ITD 9 NPM1:FLT3_ITD:DNMT3A Patients 6 FLT3_ITD:DNMT3A 20 40 log10 FDR FLT3_ITD:IDH2 NPM1 60 − KRAS NPM1:FLT3_ITD:TET2 NPM1:FLT3 TP53 FLT3_ITD:FLT3 FLT3_ITD:TET2 NRAS 3 FLT3_ITD:WT1 TP53:NRAS NPM1:IDH2 NPM1:DNMT3A ASXL1:KRAS FLT3_ITD:RUNX1 ASXL1 FLT3 NPM1:SRSF2 IDH1:DNMT3A STAG2:ASXL1 FLT3_ITD:TET2:DNMT3A NPM1:TET2 IDH2 ASXL1:SRSF2 0 SMC1A −100 −50 0 50 Average Difference Association of mutations with GDC−0879 SMC1A 3 2 Patients 20 40 log10 FDR 60 − FLT3_ITD:IDH2 NPM1:IDH2 1 0 −40 −20 0 Average Difference Association of mutations with GDC−0941 FLT3_ITD:RUNX1 1.00 0.75 Patients 20 0.50 40 log10 FDR 60 − 0.25 0.00 −40 −20 0 20 40 Average Difference Association of mutations with GSK−1838705A NPM1:IDH2 3 FLT3_ITD:IDH2 2 Patients 20 40 log10 FDR IDH2 60 − SMC1A KRAS 1 0 −75 −50 −25 0 25 Average Difference Association of mutations with GSK−1904529A 1.00 0.75 Patients 20 0.50 40 log10 FDR 60 − 0.25 0.00 −40 −20 0 20 40 Average Difference Association of mutations with GSK690693 1.00 0.75 Patients 20 0.50 40 log10 FDR 60 − 0.25 0.00 −40 −20 0 20 Average Difference Association of mutations with GW−2580 IDH2 TP53:NRAS NRAS 2.0 TP53 KRAS 1.5 Patients NPM1:IDH2 20 40 log10 FDR 1.0 60 − 0.5 0.0 −25 0 25 50 Average Difference Association of mutations with Gefitinib FLT3_ITD 4 NPM1:FLT3_ITD Patients 20 NPM1:FLT3_ITD:DNMT3A 40 60 log10 FDR − NPM1 80 FLT3_ITD:IDH2 2 NPM1:IDH2 FLT3_ITD:DNMT3A NRAS FLT3_ITD:SRSF2 NPM1:DNMT3A TP53:NRAS 0 −25 0 25 Average Difference Association of mutations with Gilteritinib (ASP−2215) 6 NPM1:FLT3_ITD FLT3_ITD 4 Patients NPM1:FLT3_ITD:DNMT3A 10 20 FLT3_ITD:DNMT3A 30 log10 FDR − 40 NPM1 2 NPM1:IDH2 NPM1:DNMT3A NRAS FLT3_ITD:TET2 NPM1:FLT3_ITD:TET2 0 −50 −25 0 25 Average Difference Association of mutations with Go6976 1.00 0.75 Patients 5.0 7.5 0.50 10.0 log10 FDR 12.5 − 15.0 0.25 0.00 −25 0 25 Average Difference Association of mutations with INK−128 4 FLT3_ITD 3 Patients 20 NPM1:FLT3_ITD 40 2 60 log10 FDR − 80 1 CEBPA 0 −50 −25 0 25 50 Average Difference Association of mutations with Ibrutinib (PCI−32765) 5 NPM1 NPM1:FLT3_ITD FLT3_ITD NPM1:DNMT3A 4 NPM1:FLT3_ITD:DNMT3A 3 Patients 20 40 log10 FDR 60 − 2 FLT3_ITD:DNMT3A FLT3_ITD:IDH2 NPM1:IDH2 DNMT3A 1 NPM1:SRSF2:IDH2 0 −50 −25 0 25 50 Average Difference Association of mutations with Idelalisib 1.00 0.75 Patients 20 0.50 40 log10 FDR 60 − 0.25 0.00 −25 0 25 Average Difference Association of mutations with Imatinib NRAS 2.0 FLT3_ITD TP53:NRAS 1.5 Patients FLT3_ITD:RUNX1 20 40 1.0 KIT 60 log10 FDR − 80 0.5 0.0 −30 0 30 60 Average Difference Association of mutations with JAK Inhibitor I FLT3_ITD 2 NPM1:FLT3_ITD Patients 20 40 60 log10 FDR − 80 1 0 −50 −25 0 25