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Home , Crenolanib, Vatalanib

Association of mutations with all drugs

Sorafenib+NPM1:FLT3_ITD KW−2449+FLT3_ITD

12 +NPM1:FLT3_ITD Crenolanib+FLT3_ITD

Sorafenib+FLT3_ITD

8

Patients 20 40 (GW786034)+NRAS 60 80 log10 overall FDR − log10 overall (PLX−4032)+NRAS

4 (AV−951)+NRAS (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 60 − log10 FDR 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 40 − log10 FDR 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 60 − log10 FDR

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 (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 (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 60 − log10 FDR

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 60 − log10 FDR 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 40 − log10 FDR 50

0.5

0.0

−60 −40 −20 0 20 40 Average Difference Association of mutations with (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 (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 IDH1 60 − log10 FDR 80 1

0

−30 0 30 60 Average Difference Association of mutations with

FLT3_ITD

NPM1:FLT3_ITD

10

FLT3_ITD:DNMT3A Patients NPM1:FLT3_ITD:DNMT3A 20 40 NPM1 60 − log10 FDR 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 (CI−1033)

FLT3_ITD:IDH2 2.0 FLT3_ITD

NPM1:FLT3_ITD

1.5

FLT3_ITD:TET2 Patients SMC1A 20 1.0 40 60 − log10 FDR

0.5

0.0

−60 −40 −20 0 20 Average Difference Association of mutations with (AZD2171)

RUNX1 FLT3_ITD:RUNX1

U2AF1

1.0

Patients 20 40 60 − log10 FDR

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 NPM1:FLT3_ITD:DNMT3A 60 − log10 FDR

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 60 − log10 FDR 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 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 60 − log10 FDR 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

PML.RARA

2.0

1.5

Patients 20 40 1.0 60 − log10 FDR

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 FLT3_ITD:IDH2 40 − log10 FDR 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

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 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 60 − log10 FDR

0.3

0.0

−50 −25 0 25 50 Average Difference Association of mutations with (XL880)

FLT3_ITD

NPM1:FLT3_ITD

9

NPM1:FLT3_ITD:DNMT3A

Patients 6 FLT3_ITD:DNMT3A 20 40 FLT3_ITD:IDH2 NPM1 60 − log10 FDR

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 60 − log10 FDR

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 60 − log10 FDR

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 IDH2 60 − log10 FDR 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 60 − log10 FDR

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 60 − log10 FDR

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 1.0 60 − log10 FDR

0.5

0.0

−25 0 25 50 Average Difference Association of mutations with

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 12.5 − log10 FDR 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 60 − log10 FDR 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

1.00

0.75

Patients 20 0.50 40 60 − log10 FDR

0.25

0.00

−25 0 25 Average Difference Association of mutations with 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 50 Average Difference Association of mutations with JNJ−28312141

FLT3_ITD 4

3

NPM1:FLT3_ITD

FLT3_ITD:RUNX1 FLT3_ITD:DNMT3A Patients 20 NPM1:FLT3_ITD:DNMT3A KRAS 40 2 NRAS 60

− log10 FDR 80

FLT3_ITD:IDH2 TP53 FLT3_ITD:FLT3 1 SRSF2:NRAS

0

−80 −40 0 40 Average Difference Association of mutations with JNJ−38877605

1.00

0.75

Patients 20 0.50 40 60 − log10 FDR

0.25

0.00

−40 −20 0 20 Average Difference Association of mutations with JNJ−7706621 NPM1

NPM1:FLT3_ITD

2

NPM1:IDH1

NPM1:IDH2 Patients 20 NPM1:FLT3_ITD:TET2 40 CEBPA 60

− log10 FDR NPM1:FLT3_ITD:DNMT3A 80 NPM1:DNMT3A 1 FLT3_ITD:DNMT3A

0

−20 0 20 Average Difference Association of mutations with JQ1

1.00

0.75

Patients 20 0.50 40 60 − log10 FDR

0.25

0.00

−40 −20 0 20 Average Difference Association of mutations with KI20227

FLT3_ITD:RUNX1

FLT3_ITD 1.5

NPM1:SRSF2:IDH2

1.0 Patients 20 40 60 − log10 FDR

0.5

0.0

−50 0 50 Average Difference Association of mutations with KU−55933

1.00

0.75

Patients 20 0.50 40 60 − log10 FDR

0.25

0.00

−40 −20 0 20 40 Average Difference Association of mutations with KW−2449 FLT3_ITD

NPM1:FLT3_ITD

10

FLT3_ITD:DNMT3A Patients FLT3_ITD:IDH2 20 40 NPM1:FLT3_ITD:DNMT3A NPM1 60

− log10 FDR 80 NPM1:IDH2 5 NPM1:SRSF2 NPM1:DNMT3A NRAS

NPM1:FLT3_ITD:TET2 NPM1:TET2 TP53:NRAS KRAS FLT3_ITD:TET2 ASXL1

NPM1:CEBPA IDH1:DNMT3A TP53 STAG2:ASXL1 FLT3_ITD:FLT3 CBFB.MYH11:NRAS NPM1:SRSF2:IDH2 FLT3_ITD:WT1 EZH2 ASXL1:SRSF2 0 FLT3_ITD:RUNX1 NPM1:FLT3 SRSF2:NRAS ASXL1:KRAS

−100 −50 0 50 Average Difference Association of mutations with LY−333531

8

FLT3_ITD

6

NPM1:FLT3_ITD Patients 20 4 40 60

− log10 FDR 80

NPM1:FLT3_ITD:TET2

FLT3_ITD:DNMT3A 2 ASXL1 FLT3_ITD:TET2 NPM1:FLT3_ITD:DNMT3A NPM1 ASXL1:SRSF2 FLT3_ITD:FLT3 SRSF2 TP53 FLT3_ITD:RUNX1

0

−25 0 25 Average Difference Association of mutations with

NPM1:IDH2

NPM1:FLT3_ITD NRAS

FLT3_ITD:IDH2 NPM1 1.5 FLT3_ITD

SMC1A

Patients 1.0 TP53:NRAS 20 40 60 − log10 FDR

0.5

0.0

−40 −20 0 20 40 Average Difference Association of mutations with Lenalidomide

NPM1:IDH2

3

Patients 10 2 20 30 − log10 FDR

FLT3_ITD

NPM1:FLT3_ITD 1 NPM1

0 −50 0 50 Average Difference Association of mutations with FLT3_ITD 5 NPM1:FLT3_ITD

NPM1:DNMT3A

NPM1:FLT3_ITD:DNMT3A

4

FLT3_ITD:DNMT3A

NPM1 Patients 3 KRAS 10 20 DNMT3A 30 40

− log10 FDR 50 2 60 FLT3_ITD:IDH2 STAG2:ASXL1 NPM1:TET2:DNMT3A NRAS IDH2 STAG2 ASXL1 1 NPM1:IDH2 ASXL1:SRSF2

0

−60 −30 0 30 60 Average Difference Association of mutations with (CEP−701)

1.00

0.75

Patients 5.0 7.5 0.50 10.0 12.5 − log10 FDR 15.0

0.25

0.00

−50 −25 0 25 50 Average Difference Association of mutations with Linifanib (ABT−869)

FLT3_ITD

4

NPM1:FLT3_ITD Patients 20 FLT3_ITD:DNMT3A 40 NPM1:FLT3_ITD:DNMT3A 60 − log10 FDR FLT3_ITD:WT1 2 TP53

FLT3_ITD:RUNX1

NPM1:FLT3_ITD:TET2 TP53:NRAS FLT3_ITD:TET2:DNMT3A

0

−80 −40 0 40 Average Difference Association of mutations with Lovastatin

1.00

0.75

Patients 10 20 0.50 30

− log10 FDR 40

0.25

0.00

−25 0 25 Average Difference Association of mutations with MGCD−265 FLT3_ITD

8

6

Patients 20

4 40 60 − log10 FDR NPM1:FLT3_ITD

FLT3_ITD:DNMT3A 2 FLT3_ITD:RUNX1 FLT3_ITD:TET2 CEBPA

FLT3_ITD:IDH2 GATA2 NPM1:FLT3_ITD:DNMT3A TP53 FLT3_ITD:WT1

RUNX1:DNMT3A 0

−60 −30 0 30 Average Difference Association of mutations with MK−2206

2.0 NPM1:IDH2

1.5

Patients 20 1.0 40 60 − log10 FDR

0.5

0.0

−40 0 40 Average Difference Association of mutations with MLN120B

NPM1:IDH2

3

2 Patients 20 40 60 − log10 FDR

1 FLT3_ITD:IDH2

0

−40 −20 0 20 Average Difference Association of mutations with MLN8054

1.00

0.75

Patients 20 0.50 40 60 − log10 FDR

0.25

0.00

−20 0 20 Average Difference Association of mutations with (AB−1010)

NRAS NPM1:IDH2 FLT3_ITD:IDH2

2

FLT3_ITD Patients 20 SMC1A 40 KRAS NPM1:FLT3_ITD TP53:NRAS 60 − log10 FDR

1 IDH2 IDH1:DNMT3A FLT3_ITD:TET2

0

−80 −40 0 40 Average Difference Association of mutations with Midostaurin

10.0 FLT3_ITD

7.5

Patients 20 5.0 40 NPM1:FLT3_ITD 60 − log10 FDR

FLT3_ITD:DNMT3A

FLT3_ITD:IDH2

2.5 NPM1:FLT3_ITD:DNMT3A NRAS KRAS FLT3_ITD:RUNX1 TP53

FLT3_ITD:FLT3

0.0

−50 0 50 Average Difference Association of mutations with (AMG−706)

FLT3_ITD:RUNX1

1.5

1.0 Patients 20 40 60 − log10 FDR

0.5

0.0

−60 −30 0 30 Average Difference Association of mutations with NF−kB Activation Inhibitor

2.0 FLT3_ITD

NRAS 1.5

TP53 NPM1:IDH2 Patients NPM1:FLT3_ITD TET2 20 1.0 40 60 − log10 FDR

0.5

0.0

−30 0 30 60 Average Difference Association of mutations with NVP−ADW742

FLT3_ITD 4

3

Patients 20 NPM1:FLT3_ITD 40 2 60 − log10 FDR

NRAS KRAS

FLT3_ITD:IDH2 1

0

−25 0 25 Average Difference Association of mutations with NVP−TAE684

8

FLT3_ITD

6

FLT3_ITD:IDH2

NPM1:FLT3_ITD Patients NPM1:IDH2 20 4 KRAS 40 FLT3_ITD:DNMT3A 60 − log10 FDR

NPM1:FLT3_ITD:DNMT3A NRAS

NPM1 ASXL1:SRSF2 FLT3_ITD:RUNX1 IDH1:DNMT3A 2 ASXL1 STAG2:ASXL1 FLT3_ITD:FLT3 DNMT3A:NRAS NPM1:SRSF2 IDH2

NPM1:SRSF2:IDH2 RAD21 TP53 ASXL1:KRAS

NPM1:FLT3 FLT3_ITD:TET2 TP53:NRAS

0 STAG2

−100 −50 0 50 Average Difference Association of mutations with (HKI−272)

FLT3_ITD 1.00 FLT3_ITD:IDH2 IDH1:DNMT3A

0.75

Patients 20 40 0.50 60

− log10 FDR 80

0.25

0.00

−60 −30 0 30 Average Difference Association of mutations with

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 Nutlin 3a

1.00

0.75

Patients 10 20 0.50 30 40 − log10 FDR 50

0.25

0.00

−20 −10 0 10 Average Difference Association of mutations with PD173955

KRAS FLT3_ITD

NRAS

2.0

1.5

Patients MLLT3.KMT2A 20 NPM1:FLT3_ITD 40 60 − log10 FDR 1.0 FLT3_ITD:IDH2

0.5

0.0

−40 0 40 Average Difference Association of mutations with PHA−665752

3 FLT3_ITD

FLT3_ITD:IDH2

NPM1:FLT3_ITD

2

NPM1:IDH2 Patients 20 ASXL1 KRAS 40 60 − log10 FDR IDH2 NRAS

NPM1:FLT3_ITD:DNMT3A FLT3_ITD:DNMT3A 1 SF3B1

0

−50 −25 0 25 Average Difference Association of mutations with PHT−427

1.00

0.75

Patients 20 0.50 40 60 − log10 FDR

0.25

0.00

−20 −10 0 10 20 Average Difference Association of mutations with PI−103 2.5 TP53:NRAS

2.0

1.5 FLT3_ITD:IDH2 Patients 20 40 60 − log10 FDR 1.0

0.5

0.0

−50 0 50 Average Difference Association of mutations with PLX−4720

NRAS CBFB.MYH11 IDH1:DNMT3A

0.9

Patients 5.0 0.6 7.5 10.0 12.5 − log10 FDR 15.0

0.3

0.0

−20 0 20 40 Average Difference Association of mutations with PP242

KRAS 1.5

FLT3_ITD

1.0 Patients 20 40 60

− log10 FDR 80

0.5

0.0

−30 0 30 60 Average Difference Association of mutations with PRT062607 FLT3_ITD

FLT3_ITD:DNMT3A 3

NPM1:FLT3_ITD:DNMT3A

NPM1:FLT3_ITD

NPM1:DNMT3A

2 Patients 20 40 60 − log10 FDR

FLT3_ITD:RUNX1

1 NPM1

0

−25 0 25 Average Difference Association of mutations with

2.0 FLT3_ITD NPM1:FLT3_ITD

NPM1:IDH2

NPM1 ASXL1

1.5

FLT3_ITD:IDH1

TRIO NPM1:FLT3_ITD:DNMT3A KRAS NRAS Patients STAG2:ASXL1 10 1.0 20 SF3B1 30

− log10 FDR 40

0.5

0.0

−40 −20 0 20 40 Average Difference Association of mutations with

2.0 NPM1:IDH2

PML.RARA

1.5

FLT3_ITD Patients 10 20 1.0 30

− log10 FDR 40

0.5

0.0

0 50 100 Average Difference Association of mutations with Pazopanib (GW786034)

FLT3_ITD NRAS

4

Patients 20 40 60 − log10 FDR FLT3_ITD:DNMT3A KRAS 80

2 FLT3_ITD:TET2 NPM1:FLT3_ITD TP53:NRAS NPM1:FLT3_ITD:DNMT3A

NPM1:FLT3_ITD:TET2

0

−25 0 25 50 Average Difference Association of mutations with Pelitinib (EKB−569)

FLT3_ITD

3 NPM1:FLT3_ITD

2 FLT3_ITD:IDH2 Patients 20 40 60 − log10 FDR

NPM1

1

0

−60 −30 0 30 Average Difference Association of mutations with (AP24534)

FLT3_ITD 6

NPM1:FLT3_ITD

4

Patients NPM1:FLT3_ITD:DNMT3A NPM1 20 40 FLT3_ITD:IDH2 60

− log10 FDR FLT3_ITD:DNMT3A 80

2 NPM1:IDH2

FLT3_ITD:WT1 TP53 FLT3_ITD:TET2 TP53:NRAS JAK2:RUNX1 FLT3_ITD:ASXL1 NPM1:DNMT3A

0

−50 0 50 Average Difference Association of mutations with (AC220)

12 FLT3_ITD

NPM1:FLT3_ITD 9

FLT3_ITD:DNMT3A

Patients NPM1:FLT3_ITD:DNMT3A 20 6 40 60 − log10 FDR

NPM1 NRAS FLT3_ITD:IDH2

FLT3_ITD:TET2 TP53:NRAS 3 NPM1:FLT3 FLT3_ITD:FLT3 KRAS NPM1:FLT3_ITD:TET2 NPM1:DNMT3A

TP53 FLT3_ITD:RUNX1 FLT3

NPM1:IDH2 0 FLT3_ITD:WT1

−50 0 50 Average Difference Association of mutations with RAF265 (CHIR−265)

1.5 FLT3_ITD

BCOR KRAS WT1 FLT3_ITD:IDH2

NPM1:FLT3_ITD

1.0

Patients 20 40 60 − log10 FDR

0.5

0.0

−60 −30 0 30 Average Difference Association of mutations with Rapamycin

1.00

0.75

Patients 20 0.50 40 60 − log10 FDR

0.25

0.00

−30 0 30 60 Average Difference Association of mutations with (BAY 73−4506)

FLT3_ITD

NPM1:FLT3_ITD

NPM1 4

NPM1:FLT3_ITD:DNMT3A

NPM1:DNMT3A

FLT3_ITD:DNMT3A TP53 Patients 20 40 NPM1:FLT3_ITD:TET2 60 − log10 FDR

2 FLT3_ITD:IDH2 NPM1:TET2

NPM1:TET2:DNMT3A TP53:NRAS FLT3_ITD:TET2 NPM1:SRSF2

NPM1:IDH2

0

−50 −25 0 25 50 Average Difference Association of mutations with Roscovitine (CYC−202)

2.0 FLT3_ITD

1.5 ZRSR2

NPM1:FLT3_ITD

NPM1:SRSF2 Patients NPM1:IDH1 20 1.0 40 60

− log10 FDR 80

0.5

0.0

−25 0 25 Average Difference Association of mutations with Ruxolitinib (INCB018424)

1.5 NPM1:IDH2 KRAS FLT3_ITD:IDH2

1.0

Patients 20 40 60 − log10 FDR

0.5

0.0

−50 −25 0 25 Average Difference Association of mutations with S31−201

1.00

0.75

Patients 20 0.50 40 60 − log10 FDR

0.25

0.00

−25 0 25 Average Difference Association of mutations with SB−431542

1.00

0.75

Patients 20

0.50 40 60

− log10 FDR 80

0.25

0.00

−50 −25 0 25 50 Average Difference Association of mutations with SGX−523

NPM1:SRSF2:IDH2

NPM1:CEBPA

NPM1:IDH2 2.0

NPM1:SRSF2 1.5

Patients 20 40 60 − log10 FDR 1.0

0.5

0.0

−50 −25 0 25 Average Difference Association of mutations with SNS−032 (BMS−387032)

1.00

0.75

Patients 20 0.50 40 60 − log10 FDR

0.25

0.00

−50 −25 0 25 50 Average Difference Association of mutations with SR9011

NPM1:IDH2

1.0

Patients 10 20 30

− log10 FDR 40

0.5

0.0

−50 −25 0 25 Average Difference Association of mutations with STO609

1.00

0.75

Patients 20 0.50 40 60 − log10 FDR

0.25

0.00

−20 −10 0 10 20 Average Difference Association of mutations with SU11274 KRAS 2.0

1.5

Patients 20 1.0 40 60 − log10 FDR

0.5

0.0

−25 0 25 Average Difference Association of mutations with Saracatinib (AZD0530)

NPM1:DNMT3A TP53 KRAS

1.5

DNMT3A MYC NPM1:FLT3_ITD:DNMT3A NPM1 TP53:NRAS NPM1:FLT3_ITD NRAS ASXL1:KRAS CBFB.MYH11 FLT3_ITD 1.0 Patients 20 40 60 − log10 FDR

0.5

0.0

−50 −25 0 25 50 Average Difference Association of mutations with Selinexor

1.00

0.75

Patients 5 10 0.50 15 20 − log10 FDR 25

0.25

0.00

−40 −20 0 20 Average Difference Association of mutations with (AZD6244)

NRAS

4

3

Patients 20 40 60 2 − log10 FDR 80

1

0

−60 −30 0 30 Average Difference Association of mutations with Sorafenib

FLT3_ITD NPM1:FLT3_ITD

10 FLT3_ITD:DNMT3A NPM1:FLT3_ITD:DNMT3A Patients NPM1:FLT3_ITD:TET2 20 40 FLT3_ITD:TET2 60

− log10 FDR FLT3_ITD:IDH2 80 NPM1 5

NPM1:TET2 NRAS KRAS FLT3_ITD:FLT3 NPM1:DNMT3A TP53:NRAS TP53 NPM1:SRSF2 NPM1:IDH2 ASXL1:KRAS FLT3_ITD:WT1 DNMT3A JAK2 FLT3_ITD:TET2:DNMT3A ASXL1:SRSF2 0 NPM1:FLT3

−100 −50 0 50 Average Difference Association of mutations with Staurosporine

1.00

0.75

Patients 5.0 7.5 10.0 0.50 12.5 − log10 FDR 15.0

0.25

−50 −25 0 25 50 Average Difference Association of mutations with Sunitinib

NPM1:FLT3_ITD FLT3_ITD

10

FLT3_ITD:DNMT3A Patients 20 NPM1:FLT3_ITD:DNMT3A 40

FLT3_ITD:IDH2 FLT3_ITD:TET2 60 − log10 FDR 80 FLT3_ITD:SRSF2 NPM1:FLT3_ITD:TET2 5

FLT3_ITD:FLT3 NRAS NPM1 KRAS NPM1:IDH2 TP53:NRAS FLT3_ITD:WT1 TP53 NPM1:SRSF2 NPM1:TET2 ASXL1 ASXL1:KRAS FLT3_ITD:TET2:DNMT3A 0 NPM1:DNMT3A FLT3_ITD:RUNX1 FLT3

−100 −50 0 50 Average Difference Association of mutations with TG100−115

1.00

0.75

Patients 20 0.50 40 60 − log10 FDR

0.25

0.00

−20 0 20 Average Difference Association of mutations with TG101348

1.00

0.75

Patients 5.0 7.5 0.50 10.0 12.5 − log10 FDR 15.0

0.25

0.00

−20 0 20 Average Difference Association of mutations with Tandutinib (MLN518)

1.00

0.75

Patients 5.0 7.5 10.0 0.50 12.5 − log10 FDR 15.0

0.25

−20 0 20 Average Difference Association of mutations with Tivozanib (AV−951) 4 NRAS

NPM1:FLT3_ITD FLT3_ITD

KRAS 3 TP53:NRAS

FLT3_ITD:DNMT3A Patients 20 2 TP53 NPM1:FLT3_ITD:DNMT3A 40 60 − log10 FDR ASXL1:KRAS FLT3_ITD:IDH2 NPM1 SRSF2:NRAS

CELSR2 1

0

−50 0 50 100 Average Difference Association of mutations with Tofacitinib (CP−690550)

1.00

0.75

Patients 20 0.50 40 60 − log10 FDR

0.25

0.00

−40 −20 0 20 40 Average Difference Association of mutations with Tozasertib (VX−680)

NPM1:FLT3_ITD FLT3_ITD 6

FLT3_ITD:IDH2

4 NPM1:FLT3_ITD:DNMT3A NPM1 NPM1:IDH2 Patients 20 FLT3_ITD:DNMT3A 40 60

− log10 FDR 80

2

0

−60 −30 0 30 Average Difference Association of mutations with (GSK1120212)

CBFB.MYH11

CBFB.MYH11:NRAS NRAS 1.5

1.0 Patients 20 40 60

− log10 FDR 80

0.5

0.0

−50 0 50 Average Difference Association of mutations with VX−745

2.5 NPM1:FLT3_ITD NPM1

NPM1:IDH2 2.0

1.5 FLT3_ITD:ASXL1 Patients 20 NPM1:FLT3_ITD:DNMT3A 40 60 − log10 FDR 1.0 FLT3_ITD

0.5

0.0

−60 −30 0 30 60 Average Difference Association of mutations with (ZD6474)

6 FLT3_ITD

NPM1:FLT3_ITD

NPM1:IDH2 4 NPM1

Patients FLT3_ITD:TET2 FLT3_ITD:IDH2 20 40 NPM1:SRSF2 60

− log10 FDR 80

2 NPM1:FLT3_ITD:TET2 NRAS NPM1:FLT3_ITD:DNMT3A

FLT3_ITD:SRSF2

0

−50 −25 0 25 Average Difference Association of mutations with Vargetef

FLT3_ITD

6

NPM1:FLT3_ITD

4

FLT3_ITD:DNMT3A Patients 20 NPM1:FLT3_ITD:DNMT3A 40 60 − log10 FDR NPM1:IDH2 KRAS FLT3_ITD:IDH2 NPM1:TET2:DNMT3A NPM1 2 FLT3_ITD:TET2:DNMT3A FLT3_ITD:TET2 NRAS NPM1:FLT3_ITD:TET2 TP53:NRAS IDH2 TP53 FLT3_ITD:FLT3 IDH1:DNMT3A

NPM1:SRSF2 ASXL1:KRAS

0

−40 0 40 Average Difference Association of mutations with Vatalanib (PTK787) 2.0 FLT3_ITD NRAS

SMC1A

FLT3_ITD:IDH2

1.5 FLT3_ITD:FLT3 KRAS NPM1:FLT3_ITD

TP53:NRAS FLT3_ITD:ASXL1

Patients MLLT3.KMT2A 20 1.0 40 60

− log10 FDR 80

0.5

0.0

−60 −30 0 30 Average Difference Association of mutations with Vemurafenib (PLX−4032)

NRAS

4

3

Patients 10 20 30 2 FLT3_ITD 40 − log10 FDR 50 60 NPM1:IDH2 NPM1 KRAS

1 FLT3_ITD:IDH2 CBFB.MYH11:NRAS NPM1:FLT3_ITD

0

−20 0 20 Average Difference Association of mutations with

PML.RARA

3

2

Patients 20 40 60 − log10 FDR SF3B1 FLT3_ITD:IDH1

1 TET2 KRAS

0

−100 −50 0 50 Average Difference Association of mutations with Vismodegib (GDC−0449)

1.00

0.75

Patients 20 0.50 40 60 − log10 FDR

0.25

0.00

−40 −20 0 Average Difference Association of mutations with Volasertib (BI−6727)

ZRSR2

1.0

Patients 10 20 30 40 − log10 FDR 50 0.5

0.0

−20 0 20 40 Average Difference Association of mutations with XAV−939

1.2 BCORL1BCOR:DNMT3A

BCOR:ASXL1 BCOR

BCOR:SRSF2

0.9

Patients 20 0.6 40 60 − log10 FDR

0.3

0.0

−60 −40 −20 0 20 Average Difference Association of mutations with YM−155 1.5 CBFB.MYH11:NRAS

NPM1:IDH1 IDH1

PML.RARA

1.0

Patients 20 40 60 − log10 FDR

0.5

0.0

−25 0 25 Average Difference Association of drugs with NPM1:DNMT3A:NRAS

CI−1040 (PD184352)

1.0

Patients 5 6 7

− log10 FDR 8 0.5

0.0

−50 −25 0 25 50 Average Difference Association of drugs with NPM1:DNMT3A:PTPN11

1.00

0.75

Patients 5.00 5.25 0.50 5.50 5.75 − log10 FDR 6.00

0.25

0.00

−25 0 25 50 Average Difference Association of drugs with NPM1:DNMT3A:FLT3

Crenolanib

1.0

Patients 5.0 5.5 6.0 6.5 − log10 FDR 7.0 0.5

0.0

−50 −25 0 25 Average Difference Association of drugs with FLT3_ITD:TET2:DNMT3A

Vargetef

Foretinib (XL880) 1.5

Sorafenib Cabozantinib

Sunitinib Patients

1.0 5.00 Linifanib (ABT−869) 5.25 5.50 5.75 − log10 FDR 6.00

0.5

0.0

−75 −50 −25 0 25 50 Average Difference Association of drugs with NPM1:TET2:DNMT3A

Regorafenib (BAY 73−4506) 1.5 Cabozantinib

Lenvatinib

Vargetef

Entospletinib (GS−9973)

1.0 Patients 5 6 7 8 − log10 FDR 9

0.5

0.0

−50 −25 0 25 50 Average Difference Association of drugs with NPM1:FLT3_ITD:DNMT3A

Sorafenib 8 Cabozantinib

KW−2449

Quizartinib (AC220) Sunitinib Foretinib (XL880) 6

Crenolanib Patients Lenvatinib Regorafenib (BAY 73−4506) 5.0 7.5 Dovitinib (CHIR−258) Tozasertib (VX−680) 10.0 4 PRT062607 Ibrutinib (PCI−32765)Vargetef 12.5

− log10 FDR NVP−TAE684 Gilteritinib (ASP−2215) Gefitinib 15.0 Midostaurin 17.5 17−AAG (Tanespimycin) LY−333531 Ponatinib (AP24534) Entospletinib (GS−9973) Pazopanib (GW786034) Linifanib (ABT−869) 2 Barasertib (AZD1152−HQPA) Erlotinib JNJ−28312141 A−674563 Vandetanib (ZD6474) JNJ−7706621 Axitinib (AG−013736) Palbociclib

Tivozanib (AV−951) VX−745 PHA−665752 Saracatinib (AZD0530) 0 MGCD−265 Bay 11−7085 Bosutinib (SKI−606)

−75 −50 −25 0 25 Average Difference Association of drugs with NPM1:FLT3_ITD:TET2

Sorafenib

6

Sunitinib Patients 5 Crenolanib 6 4 7 Quizartinib (AC220) 8 Cabozantinib Barasertib (AZD1152−HQPA) 9 − log10 FDR Dovitinib (CHIR−258) 10 LY−333531 11 Foretinib (XL880) Vandetanib (ZD6474)

2 KW−2449 Regorafenib (BAY 73−4506) Erlotinib

Vargetef Alisertib (MLN8237) JNJ−7706621

Gilteritinib (ASP−2215) A−674563

17−AAG (Tanespimycin) Pazopanib (GW786034) Linifanib (ABT−869) 0

−50 0 Average Difference Association of drugs with TP53:NRAS

Cabozantinib

Quizartinib (AC220)

3 Sunitinib Tivozanib (AV−951) Crizotinib (PF−2341066) Foretinib (XL880)

Sorafenib PI−103

GW−2580 2 Patients Pazopanib (GW786034) Dovitinib (CHIR−258) 5.00 Imatinib Regorafenib (BAY 73−4506) KW−2449 5.25 5.50 Vatalanib (PTK787) Axitinib (AG−013736) 5.75 − log10 FDR Gefitinib Saracatinib (AZD0530) Vargetef Dasatinib 6.00 NVP−TAE684 Ponatinib (AP24534) Masitinib (AB−1010) 1 Lapatinib Linifanib (ABT−869) 17−AAG (Tanespimycin)

0

−50 0 50 100 Average Difference Association of drugs with DNMT3A:NRAS

NVP−TAE684

CI−1040 (PD184352)

1.0

Patients 5.0 7.5 10.0

− log10 FDR 12.5 0.5

0.0

−50 −25 0 25 Average Difference Association of drugs with NPM1:NRAS

CI−1040 (PD184352)

1.5

Patients 5 6 1.0 7 8 9 − log10 FDR 10 11

0.5

0.0

−60 −40 −20 0 20 Average Difference Association of drugs with CBFB.MYH11:NRAS

Trametinib (GSK1120212)

1.5

YM−155 KW−2449

Vemurafenib (PLX−4032)

1.0 Patients 5.0 5.5 6.0 6.5 − log10 FDR 7.0

0.5

0.0

−50 0 50 Average Difference Association of drugs with FLT3_ITD:WT1

Sorafenib

Barasertib (AZD1152−HQPA)

Linifanib (ABT−869)

Cabozantinib 2 Sunitinib

Dovitinib (CHIR−258) Patients Crenolanib 5.00 Foretinib (XL880) 5.25 A−674563 17−AAG (Tanespimycin) 5.50 Quizartinib (AC220) 5.75 − log10 FDR 6.00 KW−2449 1 Ponatinib (AP24534)

MGCD−265

0

−80 −40 0 40 Average Difference Association of drugs with NPM1:WT1

1.00

0.75

Patients 5

0.50 6 7

− log10 FDR 8

0.25

0.00

−40 −20 0 20 Average Difference Association of drugs with ASXL1:KRAS

Cabozantinib 2.0

Foretinib (XL880)

Sunitinib

Tivozanib (AV−951) 1.5 NVP−TAE684 Sorafenib

KW−2449 Crenolanib

Vargetef Patients Saracatinib (AZD0530) 1.0 5 − log10 FDR

0.5

0.0

0 20 40 60 80 Average Difference Association of drugs with DNMT3A:PTPN11

1.00

0.75

Patients 5

0.50 6 7

− log10 FDR 8

0.25

0.00

−25 0 25 50 Average Difference Association of drugs with NPM1:PTPN11

1.00

0.75

Patients 5

0.50 6 7

− log10 FDR 8

0.25

0.00

−40 −20 0 20 40 Average Difference Association of drugs with IDH2:FLT3

1.00

0.75

Patients 5.0 5.5 0.50 6.0 6.5 − log10 FDR 7.0

0.25

0.00

−25 0 25 50 Average Difference Association of drugs with DNMT3A:FLT3 1.2

Crenolanib

0.9

Patients 5

0.6 6 7 8 − log10 FDR 9

0.3

0.0

−50 −25 0 25 50 Average Difference Association of drugs with FLT3_ITD:FLT3

6 Crenolanib

Sunitinib

4

Patients Sorafenib 5 KW−2449 6

Foretinib (XL880) 7 − log10 FDR 8 Quizartinib (AC220)

2 Dovitinib (CHIR−258) LY−333531

Vatalanib (PTK787)

JNJ−28312141

Vargetef Cabozantinib

Midostaurin NVP−TAE684

0

−90 −60 −30 0 30 Average Difference Association of drugs with NPM1:FLT3

Quizartinib (AC220)

Foretinib (XL880) 1.5 Crenolanib

KW−2449

NVP−TAE684

Entospletinib (GS−9973)

1.0 Sorafenib Patients Cabozantinib 5.0 7.5 10.0 12.5

− log10 FDR 15.0 17.5

0.5

0.0

−40 −20 0 20 Average Difference Association of drugs with SRSF2:IDH2

1.00

0.75

Patients 5.0 7.5 0.50 10.0 12.5 − log10 FDR 15.0

0.25

0.00

−50 −25 0 25 50 Average Difference Association of drugs with DNMT3A:IDH2

Entospletinib (GS−9973)

0.9

Patients 0.6 6 8 10

− log10 FDR 12

0.3

0.0

−40 −20 0 20 Average Difference Association of drugs with ASXL1:IDH2

1.00

0.75

Patients 5.00 5.25 0.50 5.50 5.75 − log10 FDR 6.00

0.25

0.00

−40 −20 0 20 40 Average Difference Association of drugs with RUNX1:IDH2

1.00

0.75

Patients 0.50 5 − log10 FDR

0.25

0.00

−75 −50 −25 0 25 Average Difference Association of drugs with BCOR:IDH2

1.00

0.75

Patients 0.50 5 − log10 FDR

0.25

0.00

−50 −25 0 25 50 Average Difference Association of drugs with FLT3_ITD:IDH2

Barasertib (AZD1152−HQPA)

7.5 Sunitinib

KW−2449 Tozasertib (VX−680) Canertinib (CI−1033)

Masitinib (AB−1010) GSK−1838705A Sorafenib Patients Vandetanib (ZD6474) Regorafenib (BAY 73−4506) 5.00 NVP−TAE684 5.0 5.25 Foretinib (XL880) Entospletinib (GS−9973) 5.50 PHA−665752 Lapatinib 5.75 − log10 FDR Dovitinib (CHIR−258) Cabozantinib Midostaurin Ruxolitinib (INCB018424) 6.00 Ponatinib (AP24534) Pelitinib (EKB−569) Erlotinib Bosutinib (SKI−606) Bay 11−7085 Gefitinib Vatalanib (PTK787) 2.5 Ibrutinib (PCI−32765) Axitinib (AG−013736) VargetefTivozanib (AV−951) Lenvatinib Quizartinib (AC220) GDC−0879 Vemurafenib (PLX−4032) A−674563 MGCD−265 17−AAG (Tanespimycin)

PI−103 DBZ RAF265 (CHIR−265) NVP−ADW742 0.0 JNJ−28312141 PD173955 Neratinib (HKI−272) MLN120B AZD1480

−100 −50 0 50 Average Difference Association of drugs with NPM1:IDH2 5

KW−2449

Vandetanib (ZD6474)

4 DBZ

NVP−TAE684 Lenalidomide Tozasertib (VX−680)

MLN120B GSK−1838705A Masitinib (AB−1010) 3 Foretinib (XL880) Patients Vargetef Barasertib (AZD1152−HQPA) Sunitinib 8 Lapatinib 10 Ponatinib (AP24534) SGX−523 Gefitinib 12 Panobinostat − log10 FDR Ibrutinib (PCI−32765) 2 Gilteritinib (ASP−2215) 14 MK−2206 PHA−665752 VX−745 Ruxolitinib (INCB018424) Palbociclib

Sorafenib GW−2580 Erlotinib JNJ−7706621

Cabozantinib Bay 11−7085 1 GDC−0879 Entospletinib (GS−9973) SR9011 NF−kB Activation Inhibitor Quizartinib (AC220) A−674563

Vemurafenib (PLX−4032) Lenvatinib 0 Regorafenib (BAY 73−4506)

−100 −50 0 50 Average Difference Association of drugs with DNMT3A:SRSF2

1.00

0.75

Patients 5.00 5.25 0.50 5.50 5.75 − log10 FDR 6.00

0.25

0.00

−20 0 20 40 Average Difference Association of drugs with IDH1:SRSF2

1.00

0.75

Patients 5.0 5.5 0.50 6.0 6.5 − log10 FDR 7.0

0.25

0.00

−20 0 20 40 Average Difference Association of drugs with ASXL1:SRSF2

Barasertib (AZD1152−HQPA)

LY−333531

1.5 Foretinib (XL880)

NVP−TAE684

KW−2449

Cabozantinib

1.0 Sorafenib Patients Lenvatinib 5.0 5.5 6.0 6.5 − log10 FDR 7.0

0.5

0.0

−20 0 20 40 60 Average Difference Association of drugs with RUNX1:SRSF2

1.00

0.75

Patients 5.0

0.50 7.5 10.0

− log10 FDR 12.5

0.25

0.00

−40 −20 0 20 Average Difference Association of drugs with TET2:SRSF2

1.00

0.75

Patients 5.0 5.5 0.50 6.0 6.5 − log10 FDR 7.0

0.25

0.00

−20 0 20 40 Average Difference Association of drugs with BCOR:SRSF2

XAV−939

0.9

Patients 0.6 5 6 7

− log10 FDR 8

0.3

0.0

−50 −25 0 25 Average Difference Association of drugs with STAG2:SRSF2

1.2 Barasertib (AZD1152−HQPA)

0.9

Patients 5.0 5.5 0.6 6.0 6.5 − log10 FDR 7.0

0.3

0.0

−20 0 20 40 Average Difference Association of drugs with GATA2:CEBPA

1.00

0.75

Patients 5.00 5.25 0.50 5.50 5.75 − log10 FDR 6.00

0.25

0.00

−30 0 30 60 Average Difference Association of drugs with TET2:CEBPA

1.00

0.75

Patients 6

0.50 7 8

− log10 FDR 9

0.25

0.00

−30 −20 −10 0 10 20 30 Average Difference Association of drugs with IDH1:DNMT3A

Foretinib (XL880) 1.5

NVP−TAE684

KW−2449

PLX−4720 Vargetef

Masitinib (AB−1010) 1.0 Patients Neratinib (HKI−272) 5 6 7 8 9 − log10 FDR 10 11 0.5

0.0

0 20 40 Average Difference Association of drugs with RUNX1:DNMT3A

MGCD−265 1.00

0.75

Patients 5.00 5.25

0.50 5.50 5.75 − log10 FDR 6.00

0.25

0.00

−40 −20 0 20 Average Difference Association of drugs with TET2:DNMT3A

1.00

0.75

Patients 5 6 7 0.50 8 9 − log10 FDR 10 11

0.25

0.00

−25 0 25 50 Average Difference Association of drugs with BCOR:DNMT3A

1.2 XAV−939

0.9

Patients 5.0 5.5 0.6 6.0 6.5 − log10 FDR 7.0

0.3

0.0

−50 −25 0 25 Average Difference Association of drugs with FLT3_ITD:DNMT3A

10.0 Sorafenib

Cabozantinib

7.5 KW−2449 Sunitinib

Quizartinib (AC220)

Crenolanib

Foretinib (XL880) Patients 5 Dovitinib (CHIR−258) Lenvatinib 5.0 10 NVP−TAE684 Vargetef 15 − log10 FDR Tozasertib (VX−680) Regorafenib (BAY 73−4506) 20 Midostaurin Pazopanib (GW786034) Gilteritinib (ASP−2215) Barasertib (AZD1152−HQPA) PRT062607 2.5 Linifanib (ABT−869) LY−333531 17−AAG (Tanespimycin) Ponatinib (AP24534) Gefitinib JNJ−28312141 CYT387 Erlotinib JNJ−7706621 Tivozanib (AV−951) PHA−665752 Ibrutinib (PCI−32765) Axitinib (AG−013736) 0.0 Bosutinib (SKI−606) A−674563 MGCD−265 Entospletinib (GS−9973)

−75 −50 −25 0 25 Average Difference Association of drugs with NPM1:DNMT3A 5 Lenvatinib

Ibrutinib (PCI−32765) 4

Cabozantinib Regorafenib (BAY 73−4506)

3 Sorafenib

KW−2449 PRT062607 Patients 10 Crenolanib 20 Entospletinib (GS−9973) 30 − log10 FDR Foretinib (XL880) 2 Saracatinib (AZD0530) Dovitinib (CHIR−258) Gefitinib

17−AAG (Tanespimycin) Axitinib (AG−013736)

Gilteritinib (ASP−2215) JNJ−7706621 1 Quizartinib (AC220) Sunitinib Ponatinib (AP24534)

0

−40 −20 0 Average Difference Association of drugs with FLT3_ITD:SF3B1

2.0 Crenolanib

1.5

Patients 5 6 1.0 7 8 − log10 FDR 9

0.5

0.0

−50 −25 0 25 Average Difference Association of drugs with NPM1:IDH1

Dovitinib (CHIR−258) JNJ−7706621

Barasertib (AZD1152−HQPA)

1.5 YM−155

Erlotinib

Roscovitine (CYC−202) Patients 5 Entospletinib (GS−9973) 1.0 6 7 8

− log10 FDR 9 10

0.5

0.0

−50 −25 0 25 Average Difference Association of drugs with RUNX1:ASXL1

1.00

0.75

Patients 5 6

0.50 7 8

− log10 FDR 9 10

0.25

0.00

−25 0 25 Average Difference Association of drugs with TET2:ASXL1

1.00

0.75

Patients 5.00 5.25 0.50 5.50 5.75 − log10 FDR 6.00

0.25

0.00

−25 0 25 50 Average Difference Association of drugs with BCOR:ASXL1

1.2 XAV−939

0.9

Patients 0.6 5 − log10 FDR

0.3

0.0

−60 −40 −20 0 20 Average Difference Association of drugs with STAG2:ASXL1

Foretinib (XL880) 1.5 Lenvatinib

KW−2449

NVP−TAE684 Erlotinib Cabozantinib

Palbociclib 1.0 Patients 5.00 5.25 5.50 5.75 − log10 FDR 6.00

0.5

0.0

−40 −20 0 20 40 60 Average Difference Association of drugs with FLT3_ITD:ASXL1

Barasertib (AZD1152−HQPA)

17−AAG (Tanespimycin) 2.0

1.5 VX−745

Vatalanib (PTK787) Patients 5 Ponatinib (AP24534) − log10 FDR 1.0

0.5

0.0

−50 −25 0 25 Average Difference Association of drugs with BCOR:RUNX1

1.00

0.75

Patients 5 6 0.50 7 8 − log10 FDR 9

0.25

0.00

−40 −20 0 20 Average Difference Association of drugs with FLT3_ITD:RUNX1

JNJ−28312141 Midostaurin

Bosutinib (SKI−606) KW−2449

Crenolanib 2.0 NVP−TAE684

MGCD−265 Cabozantinib

Motesanib (AMG−706) Dovitinib (CHIR−258)

KI20227 Foretinib (XL880) Patients 1.5 Linifanib (ABT−869) Quizartinib (AC220) 5 Cediranib (AZD2171) LY−333531 6 7 17−AAG (Tanespimycin) Sunitinib 8 PRT062607 9 − log10 FDR 1.0 GDC−0941 Imatinib 10 11

0.5

0.0

−75 −50 −25 0 Average Difference Association of drugs with FLT3_ITD:U2AF1

1.00

0.75

Patients 0.50 5 − log10 FDR

0.25

0.00

−50 −25 0 25 Average Difference Association of drugs with FLT3_ITD:TET2

Sorafenib

Sunitinib

6

Patients Crenolanib 6 4 Vandetanib (ZD6474) 8

Barasertib (AZD1152−HQPA) 10 Cabozantinib 12 − log10 FDR Pazopanib (GW786034) 14 Foretinib (XL880) Quizartinib (AC220) LY−333531 KW−2449 17−AAG (Tanespimycin) 2 Vargetef Dovitinib (CHIR−258) Canertinib (CI−1033) A−674563 Erlotinib Bosutinib (SKI−606) Regorafenib (BAY 73−4506) NVP−TAE684 AZD1480 Ponatinib (AP24534)

Gilteritinib (ASP−2215) MGCD−265 0 Masitinib (AB−1010)

−80 −60 −40 −20 0 20 Average Difference Association of drugs with NPM1:TET2

Sorafenib

3

Cabozantinib

2 Patients Regorafenib (BAY 73−4506) 10 15 Sunitinib KW−2449 20 − log10 FDR

Foretinib (XL880)

1

0

−50 −25 0 25 Average Difference Association of drugs with NPM1:FLT3_ITD

Sorafenib Sunitinib

Crenolanib KW−2449

Cabozantinib

Dovitinib (CHIR−258)

Foretinib (XL880) 10 Barasertib (AZD1152−HQPA) Quizartinib (AC220) NVP−TAE684 Vargetef PRT062607 17−AAG (Tanespimycin) Patients Ponatinib (AP24534) LY−333531 10 Erlotinib Tozasertib (VX−680) 20 Gilteritinib (ASP−2215) Lapatinib Regorafenib (BAY 73−4506) 30 − log10 FDR Vandetanib (ZD6474) Roscovitine (CYC−202) Bosutinib (SKI−606) Gefitinib 5 Canertinib (CI−1033) Midostaurin AZD1480 Ibrutinib (PCI−32765) Linifanib (ABT−869) Entospletinib (GS−9973) Crizotinib (PF−2341066) A−674563 LenvatinibPazopanib (GW786034) Pelitinib (EKB−569) JNJ−7706621 VX−745 PHA−665752 Tivozanib (AV−951) INK−128 Vatalanib (PTK787) Bay 11−7085 MGCD−265 CYT387 Palbociclib NVP−ADW742

JNJ−28312141LenalidomidePD173955NF−kB Activation InhibitorVemurafenib (PLX−4032) 0 JAK InhibitorAxitinib I (AG−013736)RAF265 (CHIRMasitinib−265) (ABAlisertib−1010) (MLN8237)Saracatinib (AZD0530)

−75 −50 −25 0 25 Average Difference Association of drugs with CSF3R

1.00

0.75

Patients 6.00 6.25 0.50 6.50 6.75 − log10 FDR 7.00

0.25

0.00

−40 −20 0 20 Average Difference Association of drugs with CELSR2 1.2 Tivozanib (AV−951)

0.9

0.6 Patients 5 − log10 FDR

0.3

0.0

−75 −50 −25 0 25 Average Difference Association of drugs with NRAS

Pazopanib (GW786034)

Selumetinib (AZD6244) Vemurafenib (PLX−4032) Quizartinib (AC220)

4 Tivozanib (AV−951) Sunitinib CI−1040 (PD184352) KW−2449 Sorafenib GW−2580 Patients NVP−TAE684 PD173955 10 Imatinib Masitinib (AB−1010) Vargetef 20 Cabozantinib 30 Erlotinib CYT387 40 − log10 FDR Foretinib (XL880) Midostaurin Gefitinib 50 2 Crizotinib (PF−2341066)JNJ−28312141 Trametinib (GSK1120212) Lapatinib

Saracatinib (AZD0530) Gilteritinib (ASP−2215) Vatalanib (PTK787) Flavopiridol Vandetanib (ZD6474) NF−kB Activation Inhibitor

Lenvatinib NVP−ADW742 PLX−4720

PHA−665752 Dovitinib (CHIR−258)

Palbociclib Entospletinib (GS−9973)

0 Crenolanib

−50 −25 0 25 50 Average Difference Association of drugs with SMC3

1.00

0.75

Patients 5.00 5.25 0.50 5.50 5.75 − log10 FDR 6.00

0.25

0.00

−50 −25 0 25 50 Average Difference Association of drugs with WT1

RAF265 (CHIR−265)

1.0

Patients 5 10 15 20 − log10 FDR 25 0.5

0.0

−20 0 20 Average Difference Association of drugs with CBL

1.00

0.75

Patients 5.0 5.5 0.50 6.0 6.5 − log10 FDR 7.0

0.25

0.00

−20 0 20 40 Average Difference Association of drugs with KRAS 4 NVP−TAE684 Sorafenib

Sunitinib

Foretinib (XL880) Cabozantinib

Crizotinib (PF−2341066) Tivozanib (AV−951) 3 Lenvatinib Vargetef KW−2449 Bosutinib (SKI−606) Pazopanib (GW786034) PD173955 Dovitinib (CHIR−258) Patients GW−2580 5.0 JNJ−28312141 2 SU11274 Quizartinib (AC220) 7.5 Ruxolitinib (INCB018424) Vatalanib (PTK787)PP242 10.0 Saracatinib (AZD0530) 12.5 − log10 FDR Midostaurin Erlotinib Crenolanib 15.0 PHA−665752 RAF265 (CHIR−265) Venetoclax NVP−ADW742 Masitinib (AB−1010) 1 Palbociclib GSK−1838705A Dasatinib Barasertib (AZD1152−HQPA)

Vemurafenib (PLX−4032)

0

−50 −25 0 25 50 Average Difference Association of drugs with PTPN11

Barasertib (AZD1152−HQPA)

1.5

Patients 5.0 1.0 7.5 10.0 12.5

− log10 FDR 15.0 17.5

0.5

0.0

−30 0 30 60 Average Difference Association of drugs with FLT3

Quizartinib (AC220)

1.5 Foretinib (XL880)

Crenolanib

Sunitinib

1.0 Patients 10 15 20 25 − log10 FDR 30

0.5

0.0

−30 −20 −10 0 10 20 Average Difference Association of drugs with PDS5B

2.0 BMS−345541

1.5

Patients 5.00 5.25 1.0 5.50 5.75 − log10 FDR 6.00

0.5

0.0

−40 −20 0 20 Average Difference Association of drugs with IDH2

GW−2580

2.0 NVP−TAE684

GSK−1838705A

Vargetef 1.5 Crizotinib (PF−2341066)

PHA−665752

DBZ Lenvatinib Patients 10 Masitinib (AB−1010) Foretinib (XL880) 20 1.0 Entospletinib (GS−9973) 30 − log10 FDR

0.5

0.0

−20 0 20 Average Difference Association of drugs with CREBBP

1.25

A−674563

1.00

0.75

Patients 5 − log10 FDR 0.50

0.25

0.00

−25 0 25 50 Average Difference Association of drugs with TP53

Dovitinib (CHIR−258)

Regorafenib (BAY 73−4506)

Sunitinib Sorafenib 3 17−AAG (Tanespimycin)

Cabozantinib

KW−2449 Patients Foretinib (XL880) Tivozanib (AV−951) GW−2580 10 2 Saracatinib (AZD0530) Linifanib (ABT−869) 15 20 Quizartinib (AC220) JNJ−28312141 − log10 FDR Crenolanib 25 LY−333531 Ponatinib (AP24534) NVP−TAE684 MGCD−265 Vargetef 1 Midostaurin NF−kB Activation Inhibitor Dasatinib

0

−50 −25 0 25 50 Average Difference Association of drugs with SRSF2

LY−333531

Crenolanib

1.0

Patients 10 20 30

− log10 FDR 40 0.5

0.0

−10 0 10 20 Average Difference Association of drugs with JAK3

1.00

0.75

Patients 0.50 5 − log10 FDR

0.25

0.00

−20 0 20 40 Average Difference Association of drugs with CEBPA

MGCD−265 1.5

JNJ−7706621

INK−128

1.0

Patients 10 15 20

− log10 FDR 25

0.5

0.0

−25 0 25 Average Difference Association of drugs with DNMT3A

2.5 Lenvatinib

2.0

1.5 Patients Ibrutinib (PCI−32765) 20 Saracatinib (AZD0530) 30 Cabozantinib 40 Sorafenib 50 − log10 FDR Entospletinib (GS−9973) 1.0 60

0.5

0.0

−30 −20 −10 0 10 Average Difference Association of drugs with SF3B1

Venetoclax 1.2

Palbociclib

PHA−665752

0.8 Patients 5.0 7.5 10.0 12.5 − log10 FDR 15.0

0.4

0.0

−40 0 40 80 Average Difference Association of drugs with IDH1 1.5

YM−155

CYT387

1.0

Patients 5 10 15 20 − log10 FDR 25

0.5

0.0

−25 0 25 50 Average Difference Association of drugs with ASXL1

KW−2449

Foretinib (XL880) 2

NVP−TAE684

Sunitinib Palbociclib LY−333531 Patients 10 PHA−665752 Cabozantinib 15 Lenvatinib 20 DBZ − log10 FDR 25 1

0

−20 0 20 40 Average Difference Association of drugs with RUNX1

Cediranib (AZD2171)

BEZ235

1.0

Patients 10 20 30 − log10 FDR

0.5

0.0

−25 0 25 Average Difference Association of drugs with U2AF1 1.25 Cediranib (AZD2171)

1.00

0.75 Patients 5.0 7.5 10.0 − log10 FDR 0.50 12.5

0.25

0.00

−40 −20 0 20 Average Difference Association of drugs with GATA2 1.2 MGCD−265

0.9

Patients 7 8 0.6 9 10

− log10 FDR 11 12

0.3

0.0

−20 0 20 40 Average Difference Association of drugs with KIT

Imatinib 1.00

0.75

Patients 5 6 0.50 7

− log10 FDR 8

0.25

0.00

−60 −40 −20 0 20 Average Difference Association of drugs with TET2 1.25 NF−kB Activation Inhibitor

Venetoclax

1.00

0.75 Patients 10 20 30 40 − log10 FDR 0.50 50

0.25

0.00

−20 0 20 40 Average Difference Association of drugs with DDX60L

1.00

0.75

Patients 0.50 5 − log10 FDR

0.25

0.00

−20 0 20 Average Difference Association of drugs with TRIO 1.2

Palbociclib

0.9

0.6 Patients 5 − log10 FDR

0.3

0.0

−40 −20 0 20 Average Difference Association of drugs with TENM2

1.00

0.75

Patients 5.00 5.25 0.50 5.50 5.75 − log10 FDR 6.00

0.25

0.00

−25 0 25 Average Difference Association of drugs with EZH2

KW−2449

0.9

Patients 5

0.6 6 7 8 9 − log10 FDR 10 11

0.3

0.0

−25 0 25 50 Average Difference Association of drugs with RAD21

NVP−TAE684 1.00

0.75

Patients 5.0 5.5 0.50 6.0 6.5 − log10 FDR 7.0

0.25

0.00

−50 −25 0 25 Average Difference Association of drugs with MYC 1.25 Saracatinib (AZD0530)

1.00

0.75

Patients 5 − log10 FDR 0.50

0.25

0.00

−40 −20 0 20 Average Difference Association of drugs with JAK2

Sorafenib

1.00

0.75

Patients 6 8

0.50 10 12 − log10 FDR 14

0.25

0.00

0 20 40 Average Difference Association of drugs with ZRSR2 1.5 Roscovitine (CYC−202)

Volasertib (BI−6727)

1.0

Patients 5 6 7 8 − log10 FDR 9

0.5

0.0

−50 −25 0 25 50 Average Difference Association of drugs with BCOR

Crizotinib (PF−2341066)

RAF265 (CHIR−265)

XAV−939

1.0

Patients 5 10 15

− log10 FDR 20

0.5

0.0

−40 −20 0 20 Average Difference Association of drugs with SMC1A

GDC−0879

3

2 Patients Vatalanib (PTK787) 5.00 5.25 GSK−1838705A Bay 11−7085 5.50 5.75 − log10 FDR Masitinib (AB−1010) Lapatinib 6.00 Canertinib (CI−1033)

1 Foretinib (XL880)

Crizotinib (PF−2341066)

0

−60 −40 −20 0 20 40 Average Difference Association of drugs with STAG2

Lenvatinib

Entospletinib (GS−9973)

1.0 NVP−TAE684

Patients 5.0 7.5 10.0 12.5 − log10 FDR 15.0 0.5

0.0

−20 0 20 Average Difference Association of drugs with BCORL1

1.2 XAV−939

0.9

Patients 0.6 5 − log10 FDR

0.3

0.0

−50 −25 0 25 Average Difference Association of drugs with PHF6

1.00

0.75

Patients 6.0 6.5 0.50 7.0 7.5 − log10 FDR 8.0

0.25

0.00

−20 0 20 40 Average Difference Association of drugs with FLT3_ITD

Sorafenib Sunitinib

Cabozantinib Crenolanib

Dovitinib (CHIR−258)

KW−2449 Quizartinib (AC220)

Foretinib (XL880)

10 Midostaurin Barasertib (AZD1152−HQPA) MGCD−265 Erlotinib LY−333531 Vargetef NVP−TAE684 Pazopanib (GW786034) Gefitinib

Gilteritinib (ASP−2215) 17−AAG (Tanespimycin) Canertinib (CI−1033) Patients 20 JNJ−28312141 Tozasertib (VX−680) Regorafenib (BAY 73−4506) 40 Ponatinib (AP24534) Vandetanib (ZD6474) Roscovitine (CYC−202) 60 − log10 FDR

Linifanib (ABT−869) Ibrutinib (PCI−32765) Crizotinib (PF−2341066) 5 Bosutinib (SKILenvatinib−606) A−674563 Pelitinib (EKB−569)

AZD1480 INK−128 Entospletinib (GS−9973) PHA−665752 Vemurafenib (PLX−4032) Palbociclib PRT062607 NVP−ADW742 Vatalanib (PTK787) DBZ TivozanibNF−kB (AV Activation−951) Inhibitor Panobinostat Bay 11−7085PD173955 CYT387 Lapatinib JAK Inhibitor I Axitinib (AG−013736)Masitinib (AB−1010)VX−745Saracatinib (AZD0530) 0 KI20227 LenalidomideRAF265 (CHIR−265)PP242 Neratinib (HKI−272)Imatinib

−60 −40 −20 0 20 40 Average Difference Association of drugs with NPM1

KW−2449

Sorafenib 6 Cabozantinib

Ibrutinib (PCI−32765)

Sunitinib Foretinib (XL880) Vandetanib (ZD6474)

4 Dovitinib (CHIR−258) Regorafenib (BAY 73−4506) Patients Lenvatinib 20 Quizartinib (AC220) Tozasertib (VX−680) 40 JNJ−7706621 Entospletinib (GS−9973) Barasertib (AZD1152−HQPA) 60 − log10 FDR 80 Ponatinib (AP24534)VX−745 Erlotinib Crenolanib 17−AAG (Tanespimycin) Gefitinib

2 DBZ Vargetef NVP−TAE684 LY−333531

Gilteritinib (ASP−2215) Palbociclib TivozanibSaracatinib (AV−951) (AZD0530) Lapatinib

Lenalidomide Axitinib (AG−013736) A−674563 Vemurafenib (PLX−4032) Pelitinib (EKB−569) PRT062607 0 Bay 11−7085

−40 −20 0 20 Average Difference Association of drugs with CBFB.MYH11

Trametinib (GSK1120212)

1.5

Saracatinib (AZD0530)

Crenolanib

PLX−4720 1.0 Patients 5.0 7.5 10.0 12.5 − log10 FDR 15.0

0.5

0.0

−60 −40 −20 0 20 40 Average Difference Association of drugs with PML.RARA

Venetoclax

3

Elesclomol

2 Patients 5 Panobinostat 6 7 YM−155 8

− log10 FDR Dasatinib 9 10

1

0

−100 −50 0 50 100 Average Difference Association of drugs with MLLT3.KMT2A

1.25 PD173955

Vatalanib (PTK787)

1.00

Patients 0.75 5 6 7 8 9 − log10 FDR 0.50 10 11

0.25

0.00

−40 −20 0 20 40 60 Average Difference Association of drugs with GATA2.MECOM

1.00

0.75

Patients 5

0.50 6 7

− log10 FDR 8

0.25

0.00

−40 −20 0 20 Average Difference Association of drugs with RUNX1.RUNX1T1

1.00

0.75

Patients 5.0 5.5 0.50 6.0 6.5 − log10 FDR 7.0

0.25

0.00

−40 −20 0 20 40 Average Difference Association of drugs with NPM1:SRSF2:IDH2

KW−2449 SGX−523

AZD1480

2.0

1.5 Patients NVP−TAE684 5.00 KI20227 5.25 DBZ 5.50 5.75 − log10 FDR 1.0 Ibrutinib (PCI−32765) 6.00

0.5

0.0

−50 0 50 Average Difference Association of drugs with SRSF2:NRAS

CYT387

1.5 Tivozanib (AV−951)

Crenolanib

JNJ−28312141

KW−2449 1.0

Patients 5 − log10 FDR

0.5

0.0

−25 0 25 50 75 Average Difference Association of drugs with ASXL1:NRAS

1.00

0.75

Patients 0.50 5 − log10 FDR

0.25

0.00

−60 −30 0 30 Average Difference Association of drugs with NPM1:SRSF2 3 Vandetanib (ZD6474)

KW−2449

Cabozantinib

Sunitinib

2 Sorafenib

SGX−523 Patients AZD1480 5 Regorafenib (BAY 73−4506) NVP−TAE684 6 7

− log10 FDR Foretinib (XL880) Vargetef 8 Roscovitine (CYC−202) Barasertib (AZD1152−HQPA) 1

0

−80 −40 0 40 Average Difference Association of drugs with NPM1:CEBPA

KW−2449

SGX−523

2

Patients 5 − log10 FDR

1 Crizotinib (PF−2341066)

0

−50 0 50 Average Difference Association of drugs with FLT3_ITD:IDH1

Palbociclib

Entospletinib (GS−9973)

DBZ

Venetoclax

1.0

Patients 5 − log10 FDR

0.5

−75 −50 −25 0 Average Difference Association of drugs with RUNX1:SF3B1

1.00

0.75

Patients 0.50 5 − log10 FDR

0.25

0.00

−25 0 25 Average Difference Association of drugs with NPM1:IDH1:DNMT3A

1.00

0.75

Patients 5.00 5.25 0.50 5.50 5.75 − log10 FDR 6.00

0.25

0.00

−20 −10 0 10 20 Average Difference Association of drugs with WT1:NRAS

1.00

0.75

Patients 5.00 5.25 0.50 5.50 5.75 − log10 FDR 6.00

0.25

0.00

0 10 20 30 40 Average Difference Association of drugs with FLT3:NRAS

1.00

0.75

Patients 5.00 5.25 0.50 5.50 5.75 − log10 FDR 6.00

0.25

0.00

−40 −20 0 20 Average Difference Association of drugs with IDH1:NRAS

1.00

0.75

Patients 5.00 5.25 0.50 5.50 5.75 − log10 FDR 6.00

0.25

0.00

0 20 40 Average Difference Association of drugs with JAK2:RUNX1

Ponatinib (AP24534)

0.9

0.6 Patients 5 − log10 FDR

0.3

0.0

0 25 50 Average Difference Association of drugs with STAG2:TET2

1.00

0.75

Patients 0.50 5 − log10 FDR

0.25

0.00

−10 0 10 20 30 Average Difference Association of drugs with IKZF1

1.00

0.75

Patients 0.50 5 − log10 FDR

0.25

0.00

0 10 20 30 40 50 Average Difference Association of drugs with FLT3_ITD:SRSF2

5 Sunitinib

4

3

Patients 5 − log10 FDR 2 Gefitinib

Crizotinib (PF−2341066)

1 Vandetanib (ZD6474)

0

−75 −50 −25 0 Average Difference Association of drugs with NPM1:FLT3_ITD:FLT3

5 Crenolanib

4

3

Patients 5 − log10 FDR

2

1

0 −100 −75 −50 −25 0 Average Difference Association of drugs with IDH1:DNMT3A:NRAS

1.00

0.75

Patients 0.50 5 − log10 FDR

0.25

0.00

0 5 10 15 20 Average Difference Association of drugs with NPM1:IDH2:FLT3

1.00

0.75

Patients 0.50 5 − log10 FDR

0.25

0.00 −25 0 25 50 Average Difference Association of drugs with RHNO1

1.00

0.75

Patients 0.50 5 − log10 FDR

0.25

0.00

−20 −10 0 Average Difference Association of drugs with TPTE2

1.00

0.75

Patients 0.50 5 − log10 FDR

0.25

0.00

−40 −20 0 20 Average Difference Association of drugs with PUF60

1.00

0.75

Patients 0.50 5 − log10 FDR

0.25

0.00

−10 0 10 20 Average Difference Association of drugs with ACAN

1.0

0.8

Patients 5 − log10 FDR

0.6

0.4

0 10 20 30 Average Difference Association of drugs with ADAMTS7

1.00

0.75

Patients 0.50 5 − log10 FDR

0.25

0.00

−20 −10 0 Average Difference