Supplementary Tables
Supplementary Table S1. Treatment protocols pediatric AML patients.
Number of Treatment patients ADE-based regimen 64 ADE with bortezomib 14 ADE with mylotarg 6 APL-like treatment 2 TMD-like treatment 1 Relapse therapy 2 Misc treatment/novel agents 5 Unknown 2
Supplemental Table S2: Patient characteristics for the 73 pediatric acute lymphoblastic leukemia patients
Characteristics N, % Number of cases 73 ALL subtype Pre-B ALL 57 (78) T-ALL 16 (22) Age, y, median (range) 7.3 (0.2-18.0) Gender Male 40 (55) Female 33 (45) Declared Ethnicity Caucasian 61 (84) Hispanic 44 (72) Non-Hispanic 17 (28) Black American 6 (8) Asian 4 (5) Mixed 2 (3) Hispanic 1 (1) ‘‘SNP’’ Ethnicity European 9 (12) African 6 (8) American Indian 38 (52) Asian 1 (1) Not done 19 (26) Cytogenetics Favorable 15 (21) Intermediate 42 (58) Unfavorable 15 (21) Unknown 1 (1) Risk Group Low Risk 4 (5) Standard/ Intermediate Risk 29 (40) High/Very High Risk 40 (55) CNS status CNS-1 46 (63) CNS-2 20 (27) CNS-3 6 (8) Unknown 2 (3) Response Complete remission 67 (92) Resistant 4 (5) Fail 2 (3) Alive 63 (86)
Supplementary Table S3. The table shows the ‘‘Rosetta Stone’’ of the antibody and protein nomenclature, and the R2 for the antibody validation and the primary and secondary antibody dilutions. Secondary, all antibodies that were used in combination with information about the manufacturer of each antibody, the antibody source, and catalog number are listed.
Functional Protein Name Rosetta Stone RPPA Staining Details Category Functional Effect Common Name RPPA Antibody Huge Name (added MiMI Antibody R2, WB vs. Antibody 2nd Ab Full Name/Description from GeneCards of Mfg Claimed Manufacturer Catalog# Functional Group Name with PTMs) Name Source RPPA Dilution dilution Phosphorylation Target
AKT1 AKT1 AKT1 v-akt murine thymoma viral oncogene homolog 1 AKT1 Cell Signaling 9272 Rabbit > 0.7 200 15000 PI3KAKT
AKT1/AKT2/AKT3 AKT1_2_3.pS473 AKT1 v-akt murine thymoma viral oncogene homolog 1 Activation AKT-P473(Ser) Cell Signaling 9271 Rabbit > 0.7 150 20000 PI3KAKT Phospho Ser473 AKT1/AKT2/AKT3 AKT1_2_3.pT308 AKT1 v-akt murine thymoma viral oncogene homolog 1 Activation AKT-P308(Thr) Cell Signaling 9275 Rabbit > 0.7 200 20000 PI3KAKT Phospho Thr308
ASNS ASNS ASNS asparagine synthetase (glutamine-hydrolyzing) ASNS Sigma HPA029318 Rabbit 0.5-0.7 800 20000 Metabolic
ATF3 ATF3 ATF3 activating transcription factor 3 ATF3 Abcam ab87213 Rabbit > 0.7 500 20000 Autophagy, CREB
BAD BAD BAD BCL2-associated agonist of cell death Bad Cell Signaling 9292 Rabbit > 0.7 100 20000 BH3
BAK1 BAK1 BAK1 BCL2-antagonist/killer 1 Bak Cell Signaling 3814 Rabbit 0.5-0.7 100 20000 BH3
BAX BAX BAX BCL2-associated X protein Bax Cell Signaling 2772 Rabbit > 0.7 200 20000 BH3
BCL2 BCL2 BCL2 B-cell CLL/lymphoma 2 Bcl2 DAKO M0887 Mouse > 0.7 300 20000 BH3
BCL2L1 BCL2L1 BCL2L1 BCL2-like 1 Bcl-XL Cell Signaling 2762 Rabbit > 0.7 200 20000 BH3
BCL2L11 BCL2L11 BCL2L11 BCL2-like 11 (apoptosis facilitator) Bim Epitomics 1036-1 Rabbit > 0.7 200 20000 BH3
BECN1 BECN1 BECN1 beclin 1, autophagy related Beclin-1 Cell Signaling 3738 Rabbit > 0.7 500 20000 Autophagy, CREB
BID BID BID BH3 interacting domain death agonist Bid Cell Signaling 2002 Rabbit 0.5-0.7 300 20000 BH3
BIRC2 BIRC2 BIRC2 baculoviral IAP repeat containing 2 CIAP-1 Upstate 07-759 Rabbit 0.5-0.7 500 20000 IAP
XIAP XIAP BIRC4 X-linked inhibitor of apoptosis XIAP Cell Signaling 2042 Rabbit > 0.7 400 20000 IAP
BIRC5 BIRC5 BIRC5 baculoviral IAP repeat containing 5 Survivin Cell Signaling 2802 Rabbit ? 100 20000 IAP
BMI1 BMI1 BMI1 BMI1 polycomb ring finger oncogene Bmi-1 Cell Signaling 2830 Rabbit 0.5-0.7 200 20000 Histone
BRAF BRAF BRAF v-raf murine sarcoma viral oncogene homolog B Raf-B Santa Cruz sc5284 Mouse 0.5-0.7 200 20000 MEK
BRCA2 BRCA2 BRCA2 BRCA2, DNA Repair Associated BRCA2 CellSignaling 9012 Rabbit 0.5-0.7 100 20000 HIPPO
CASP3 CASP3 CASP3 caspase 3, apoptosis-related cysteine peptidase caspase 3 Cell Signaling 9662 Rabbit 0.5-0.7 1000 20000 ApopOccur
Caspase 3 cleaved CASP3.cl175 CASP3 Cleaved CASP3 caspase 3, apoptosis-related cysteine peptidase Cell Signaling 9664 Rabbit 0.5-0.7 100 20000 ApopOccur Asp175 Caspase 7 cleaved CASP7.cl198 CASP7 Cleaved Asp198 CASP7 caspase 7, apoptosis-related cysteine peptidase Cell Signaling 9491 Rabbit 0.5-0.7 300 20000 ApopOccur Asp198
CASP8 CASP8 CASP8 caspase 8, apoptosis-related cysteine peptidase Caspase 8 Cell Signaling 9746 Mouse ? 1000 20000 ApopOccur
CASP9 CASP9 CASP9 caspase 9, apoptosis-related cysteine peptidase Caspase 9 BD Pharmingen 551246 Mouse 0.5-0.7 150 20000 ApopOccur
Caspase 9 cleaved CASP9.cl315 CASP9 Cleaved Asp315 CASP9 caspase 9, apoptosis-related cysteine peptidase Cell Signaling 9505 Rabbit ? 200 20000 ApopOccur Asp315 Caspase 9 cleaved CASP9.cl330 CASP9 Cleaved Asp330 CASP9 caspase 9, apoptosis-related cysteine peptidase Cell Signaling 9501 Rabbit ? 200 20000 ApopOccur Asp330
CAV1 CAV1 CAV1 caveolin 1, caveolae protein, 22kDa Caveolin-1 Cell Signaling 3238 Rabbit > 0.7 150 20000 Adhesion
CBL CBL CBL Cbl proto-oncogene, E3 ubiquitin protein ligase Cbl-c BD Transduction Lab 610441 Mouse 0.5-0.7 1000 20000 Ubiquitin
CCNB1 CCNB1 CCNB1 cyclin B1 Cyclin B1 Santa Cruz SC245 Mouse > 0.7 150 20000 CellCycle
CCND1 CCND1 CCND1 cyclin D1 Cyclin D1(M-20) Santa Cruz sc718 Rabbit > 0.7 400 20000 CellCycle
CCND3 CCND3 CCND3 cyclin D3 Cyclin D3 Cell Signaling 2936 Mouse > 0.7 150 20000 CellCycle
CCNE1 CCNE1 CCNE1 cyclin E1 Cyclin E Santa Cruz sc-247 Mouse > 0.7 200 20000 CellCycle
CCNE2 CCNE2 CCNE2 cyclin E2 Cyclin E2 Epitomics 1142-1 Rabbit ? 300 20000 CellCycle
CD74 molecule, major histocompatibility complex, CD74 CD74 CD74 CD74 Santa Cruz sc-6262 Mouse 0.5-0.7 150 20000 T-cell class II invariant chain
CDK1 CDK1 CDC2 cyclin-dependent kinase 1 CDC2 Calbiochem cc01 Mouse 0.5-0.7 200 20000 CellCycle
CDK2 CDK2 CDK2 cyclin-dependent kinase 2 CDK2 Santa Cruz SC6248 Mouse > 0.7 200 20000 CellCycle
CDK4 CDK4 CDK4 cyclin-dependent kinase 4 CDK4 Cell Signaling 2906 Mouse > 0.7 200 20000 CellCycle
CDKN1A CDKN1A CDKN1A cyclin-dependent kinase inhibitor 1A (p21, Cip1) P21/Waf Cell Signaling 2946 Mouse ? 400 20000 CellCycle
CDKN1B CDKN1B CDKN1B cyclin-dependent kinase inhibitor 1B (p27, Kip1) P27 Santa Cruz sc-528 Rabbit > 0.7 250 20000 CellCycle
CDKN1B.pS10 CDKN1B Phospho Ser10 CDKN1B cyclin-dependent kinase inhibitor 1B (p27, Kip1) Apoptosis altered P27ps10 Epitomics 2187-1 Rabbit > 0.7 500 20000 CellCycle
CDKN2A CDKN2A CDKN2A cyclin-dependent kinase inhibitor 2A P16 Santa Cruz sc468 Rabbit > 0.7 10000 20000 CellCycle
caseinolytic mitochondrial matrix peptidase CLPP CLPP CLPP CLPP Abcam ab124822 Rabbit > 0.7 1000 20000 Histone proteolytic subunit
CREB1 CREB1 CREB1 cAMP responsive element binding protein 1 CREB Epitomics 1496-1 Rabbit > 0.7 2000 20000 CREB
CREB1.pS133 CREB2 Phospho Ser133 CREB1 cAMP responsive element binding protein 1 Activation CREB-p(ser133) Epitomics 1113-1 Rabbit 0.5-0.7 2000 20000 CREB
catenin (cadherin-associated protein), alpha 1, CTNNA1 CTNNA1 CTNNA1 Catenin-alpha Thermo CA1030 Mouse ? 300 20000 WNT 102kDa catenin (cadherin-associated protein), beta 1, CTNNB1 CTNNB1 CTNNB1 Catenin-beta Cell Signaling 9562 Rabbit > 0.7 150 20000 WNT 88kDa Histone, RPS6, DDX17 DDX17 DDX17 DEAD-Box Helicase 17 DDX17 Abcam ab180190 Rabbit 0.5-0.7 2000 20000 Transcription
DIABLO DIABLO DIABLO blo, IAP-binding mitochondrial protein Smac/Diablo Cell Signaling 2954 Mouse ? 5000 20000 IAP
H00001745- DLX1 DLX1 DLX1 distal-less homeobox 1 DLX1 Abnova Mouse 0.5-0.7 1500 20000 Transcription M01
DUSP6 DUSP6 DUSP6 dual specificity phosphatase 6 DUSP6 Abcam ab76310 Rabbit > 0.7 5000 20000 MEK
EGFR EGFR EGFR Epiidermal growth factor receptor EGFR Santa Cruz sc-03 Rabbit > 0.7 500 20000 mTOR, STP
H00005610- EIF2AK2 EIF2AK2 EIF2AK2 ryotic translation initiation factor 2-alpha kinase 2 PRKR(EIF2AK2) Abnova Mouse 0.5-0.7 10000 20000 Transcription M02 EIF2AK2 Phospho EIF2AK2.pT451 EIF2AK2 ryotic translation initiation factor 2-alpha kinase 2 Activation PRKRpTh451(EIF2AK2) Invitrogen 44-668G Rabbit ? 3000 20000 Transcription Thr451 eukaryotic translation initiation factor 2, subunit 1 EIF2S1 EIF2S1 EIF2S1 elF2 Cell Signaling 9722 Rabbit 0.5-0.7 4000 20000 Transcription alpha, 35kDa eukaryotic translation initiation factor 2, subunit 1 EIF2S1.pS51. EIF2S1 Phospho Ser51 EIF2S1 Stabalizes phospho-eIF2-alpha Cell Signaling 9721 Rabbit > 0.7 200 20000 Transcription alpha, 35kDa
EIF4E EIF4E EIF4E otic translation initiation factor 4E eIF4E Cell Signaling 9742 Rabbit > 0.7 800 20000 Transcription
ELK1.pS383 ELK1 Phospho Ser383 ELK1 ELK1, member of ETS oncogene family Activation ElK(phospho-ser383) Cell Signaling 9181 Rabbit 0.5-0.7 150 20000 MEK, PI3KAKT
v-erb-b2 avian erythroblastic leukemia viral ERBB2 ERBB2 ERBB2 HER2/Erb2 Cell Signaling 2242 Rabbit > 0.7 300 20000 STP oncogene homolog 2 v-erb-b2 avian erythroblastic leukemia viral ERBB2.pY1248 ERBB2 Phospho Tyr1248 ERBB2 Activation HER2(p-Tyr1248) Upstate 06-229 Rabbit 0.5-0.7 2000 20000 STP oncogene homolog 2
IRE1 ERN1 ERN1 Endoplasmic reticulum to nucleus signaling 1 IRE1 Cell Signaling 3294 Rabbit 0.5-0.7 1000 20000 Ubiquitin
FLI1 Fli1 FLI1 Fli-1 proto-oncogene, ETS transcription factor Fli Dennis Watson Rabbit > 0.7 4000 20000 FLI1, Histone
FN1 FN1 FN1 fibronectin 1 Fibronectin Epitomics 1574 Rabbit > 0.7 20000 20000 Adhesion
FKHRL1/FoxO3a (P- FOXO3-phospho FOXO3 forkhead box O3 Inactivation FoxO3a Cell Signaling 9465 Rabbit 0.5-0.7 20000 20000 CellCycle, PI3KAKT Ser 318/321) Ser318/321
FOXO3A FOXO3 FOXO3 forkhead box O3 FoxO3a Cell Signaling 9467 Rabbit 0.5-0.7 500 20000 CellCycle, PI3KAKT
mechanistic target of rapamycin (serine/threonine MTOR.pS2448 MTOR-phospho Ser2448 FRAP1 Activation mTor(p-Ser2448) Cell Signaling 2971 Rabbit 0.5-0.7 200 20000 mTOR kinase) mechanistic target of rapamycin (serine/threonine MTOR MTOR FRAP1 mTor Cell Signaling 2983 Rabbit > 0.7 300 20000 mTOR kinase)
GAB2 GAB2 GAB2 GRB2-associated binding protein 2 Gab2 Cell Signaling 3239 Rabbit > 0.7 800 20000 PI3KAKT Tyr452 is a potential GAB2.pY452 GAB2 Phospho Tyr452 GAB2 GRB2-associated binding protein 2 binding site of p85, Gab2-pTyr452 Cell Signaling 3882 Rabbit 0.5-0.7 75 20000 PI3KAKT the regulatory GATA binding protein 1 (globin transcription Differentiation, GATA1 GATA1 GATA1 GATA-1 Cell Signaling 3535 Rabbit > 0.7 2000 20000 factor 1) Transcription Differentiation, GATA3 GATA3 GATA3 GATA binding protein 3 GATA-3 BD Bioscience 558686 Mouse > 0.7 800 20000 Transcription
GRP78 GRP78 GRP78 Heat shock protein family A (Hsp70) member 5 GRP78 BD Transduction Lab 610978 Mouse > 0.7 1000 20000 Heatshock, Ubiquitin
HDAC1 HDAC1 HDAC1 histone deacetylase 1 HDAC1 Imgenex IM-337 Rabbit 0.5-0.7 1000 20000 Histone
HDAC2 HDAC2 HDAC2 histone deacetylase 2 HDAC2 Santa Cruz sc-7899 Rabbit > 0.7 2000 20000 Histone
HDAC3 HDAC3 HDAC3 histone deacetylase 3 HDAC3 Cell Signaling 2632 Rabbit 0.5-0.7 150 20000 Histone
HDAC6 HDAC6 HDAC6 histone deacetylase 6 HDAC6 Cell Signaling 7558 Rabbit > 0.7 20000 20000 Histone
hypoxia inducible factor 1, alpha subunit (basic HIF1A HIF1A HIF1A HIF-1α BD Pharmingen 610959 Mouse 0.5-0.7 75 20000 Hypoxia helix-loop-helix transcription factor)
H3histone HIST3H3 HIST3H3 histone cluster 3, H3 H3histone Active Motif 39163 Rabbit > 0.7 30000 20000 Histone
H3K27Me3 HIST3H3-K27-Me3 HIST3H3 histone cluster 3, H3 , Lysine 27 methylation 3 Repression H3K27Me3 Active Motif 61017 Mouse > 0.7 4000 20000 Histone
H3K4Me2 HIST3H3-K4-Me2 HIST3H3 histone cluster 3, H3 , Lysine 4 methylation 2 Repression H3K4Me2 Active Motif 39141 Rabbit > 0.7 8000 20000 Histone
H3K4Me3 HIST3H3-K4-Me3 HIST3H3 histone cluster 3, H3 , Lysine 4 methylation 3 Repression H3K4Me3 Active Motif 39159 Rabbit 0.5-0.7 10000 20000 Histone HNRNPK HNRNPK HNRPK rogeneous nuclear ribonucleoprotein K hnRNPK Santa Cruz sc-28380 Mouse 0.5-0.7 10000 20000 Histone
HSPB1 HSPB1 HSPB1 heat shock 27kDa protein 1 HSP27 Cell Signaling 2402 Mouse 0.5-0.7 400 20000 Heatshock
IGF1R IGF1R IGF1R insulin-like growth factor 1 receptor IGF-1 receptor beta Cell Signaling 3027 Rabbit 0.5-0.7 1500 20000 STP
IGFBP2 IGFBP2 IGFBP2 insulin-like growth factor binding protein 2, 36kDa IGFBP-2 Cell Signaling 3922 Rabbit > 0.7 150 20000 Adhesion
INPP5D INPP5D INPP5D inositol polyphosphate-5-phosphatase, 145kDa SHIP1 Santa Cruz SC-8425 Mouse 0.5-0.7 50 20000 mTOR
INPPL1 INPPL1 INPPL1 inositol polyphosphate phosphatase-like 1 SHIP2 Cell Signaling 2730 Rabbit > 0.7 200 20000 mTOR
IRS1.pS1101 IRS1 Phospho Ser1101 IRS1 insulin receptor substrate 1 Inhibition IRS-1-p(ser1101) Cell Signaling 2385 Rabbit > 0.7 300 20000 mTOR, TP53
integrin, alpha 2 (CD49B, alpha 2 subunit of VLA-2 ITGA2 ITGA2 ITGA2 CD49b BD Transduction Lab 611016 Mouse > 0.7 500 20000 Adhesion receptor) integrin, alpha L (antigen CD11A (p180), ITGAL ITGAL ITGAL lymphocyte function-associated antigen 1; alpha CD11a BD Transduction Lab 610826 Mouse > 0.7 500 20000 Adhesion polypeptide) integrin, beta 3 (platelet glycoprotein IIIa, antigen ITGB3 ITGB3 ITGB3 Integrin-beta3 Cell Signaling 4702 Rabbit ? 300 20000 Adhesion CD61)
JUN.pS73 JUN Phospho Ser73 JUN jun proto-oncogene Activation Jun-C-phospho ser73 Cell Signaling 9164 Rabbit > 0.7 150 20000 Transcription
JUNB JUNB JUNB jun B proto-oncogene Jun-B Cell Signaling 3755 Rabbit > 0.7 150 20000 Transcription
KDM1A KDM1A KDM1A lysine (K)-specific demethylase 1A LSD1 Cell Signaling 2184 Rabbit > 0.7 4000 20000 Histone
kinase insert domain receptor (a type III receptor KDR KDR KDR VEGFR2 Cell Signaling 2479 Rabbit > 0.7 1000 20000 Hypoxia tyrosine kinase) v-kit Hardy-Zuckerman 4 feline sarcoma viral KIT KIT KIT Kit-C Epitomics 1522 Rabbit > 0.7 1500 20000 MEK, STP oncogene homolog
LCK LCK LCK lymphocyte-specific protein tyrosine kinase Lck Cell Signaling 2752 Rabbit > 0.7 800 20000 T-cell
LEF1 LEF1 LEF1 lymphoid enhancer-binding factor 1 LEF1 Cell Signaling 2230 Rabbit > 0.7 1500 20000 WNT
LGALS3 LGALS3 LGALS3 lectin, galactoside-binding, soluble, 3 Galectin-3 Santa Cruz sc-32790 Mouse ? 400 20000 T-cell
v-yes-1 Yamaguchi sarcoma viral related LYN LYN LYN Lyn Cell Signaling 2732 Rabbit > 0.7 300 20000 MEK, STP oncogene homolog
MAP2K1 MAP2K1 MAP2K1 mitogen-activated protein kinase kinase 1 MEK Cell Signaling 9122 Rabbit > 0.7 8000 20000 MAPK
MAPK1 MAPK1 MAPK1 mitogen-activated protein kinase 1 Erk2 Santa Cruz Sc-154 Rabbit > 0.7 2000 20000 MAPK
MAPK14 MAPK14 MAPK14 mitogen-activated protein kinase 14 P38 Cell Signaling 9212 Rabbit > 0.7 1000 20000 MAPK
MAPK14.pT180Y182 MAPK14-p180p182 MAPK14 mitogen-activated protein kinase 14 Activation P38p180p182 Cell Signaling 9211 Rabbit > 0.7 200 20000 MAPK
MAPK9 MAPK9 MAPK9 mitogen-activated protein kinase 9 JNK2 Cell Signaling 4672 Rabbit 0.5-0.7 75 20000 MAPK, STAT
MCL1 MCL1 MCL1 myeloid cell leukemia sequence 1 (BCL2-related) MCL1 BD Pharmingen 559027 Mouse > 0.7 100 20000 BH3
MDM2 MDM2 MDM2 MDM2 oncogene, E3 ubiquitin protein ligase MDM2 Santa Cruz sc813 Rabbit 0.5-0.7 8000 20000 TP53
MDM4 MDM4 MDM4 Mdm4 p53 binding protein homolog (mouse) MDM4 Bethly lab A300-287A Rabbit > 0.7 8000 20000 TP53
MET.pY1230_1234_1 MET-phospho C-Met-pTyr MET met proto-oncogene Activation Biosource 44-888G Rabbit > 0.7 500 20000 STP 235 Py1230/1234/1235 1230/1234/1235 MSI2 MSI2 MSI2 Musashi RNA binding protein 2 MSI2 Chemicon MAB10085 Mouse 0.5-0.7 800 20000 RPS6
v-myc avian myelocytomatosis viral oncogene MYC MYC MYC Myc Cell Signaling 9402 Rabbit > 0.7 500 20000 CellCycle, Transcription homolog
NCL NCL NCL nucleolin C23 (nucleolin) Santa Cruz sc8031 Mouse > 0.7 400 20000 FLI1, Histone
NF2 NF2 NF2 neurofibromin 2 (merlin) NF2 Santa Cruz sc332 Rabbit 0.5-0.7 800 20000 Cytoskeletal, HIPPO
NF2.pS518 NF2-phospho ser518 NF2 neurofibromin 2 (merlin) Inactivation pNF2(ser518) Chemicon AB5607 Rabbit ? 800 20000 Cytoskeletal, HIPPO
v-rel avian reticuloendotheliosis viral oncogene RELA RELA NFKB1 NF-kB p65 Cell Signaling 3034 Rabbit 0.5-0.7 800 20000 PKC homolog A NOTCH1 cleaved Notch1-cleaved NOTCH1.cl1744 NOTCH1 notch 1 Activation Cell Signaling 4147 Rabbit > 0.7 600 20000 T-cell val1744 (Val1744)
NOTCH3 NOTCH3 NOTCH3 notch 3 Notch3 Santa Cruz sc5593 Rabbit 0.5-0.7 800 20000 T-cell
nucleophosmin (nucleolar phosphoprotein B23, NPM1.3542 NPM1mut AA3542 NPM1 NPM1.3542 Cell Signaling 3542 Rabbit 0.5-0.7 1000 20000 FLI1 numatrin)
NR4A1 NR4A1 NR4A1 nuclear receptor subfamily 4, group A, member 1 Nur77 Imgenex IMG-528 Rabbit ? 1000 20000 Transcription
NRP1 NRP1 NRP1 neuropilin 1 NRP1(neuropilin) Santa Cruz SC-5307 Mouse ? 75 20000 Cytoskeletal
ODC1 ODC1 ODC1 ornithine decarboxylase 1 ODC Shantz/Lisa Lab ? 800 20000 Metabolic
Private- PARK7 PARK7 PARK7 parkinson protein 7 DJ-1 Dr. Tek Mak Rabbit > 0.7 3000 20000 Autophagy Andreeff
PARP1 PARP1 PARP1 poly (ADP-ribose) polymerase 1 PARP Cell Signaling 9542 Rabbit 0.5-0.7 300 20000 ApopOccur
PARP1.cl214 PARP1-cleaved Asp 214 PARP1 poly (ADP-ribose) polymerase 1 Activation PARP(cleaved Asp214) Cell Signaling 9541 Rabbit > 0.7 150 20000 ApopOccur
PDK1 PDK1 PDK1 pyruvate dehydrogenase kinase, isozyme 1 PDK1 Cell Signaling 3062 Rabbit > 0.7 300 20000 mTOR
PDK1.pS241 PDK1-phospho ser241 PDK1 pyruvate dehydrogenase kinase, isozyme 1 Activation PDK1-p241(Ser) Cell Signaling 3061 Rabbit > 0.7 800 20000 mTOR
phosphotidylinositol-4,5-bisphosphate 3-kinase, PIK3CA PIK3CA PIK3CA PI3 K p110-alpha Epitomics 1683-1 Rabbit 0.5-0.7 400 20000 mTOR catalytic subunit alpha phosphoinositide-3-kinase, regulatory subunit 1 PIK3R1_2 PIK3R1/PIK3R2 PIK3R1 PI3 K p85 Cell Signaling 4292 Rabbit ? 150 20000 mTOR (alpha)
PIM1 PIM1 PIM1 pim-1 oncogene PIM1 Santa Cruz sc-13153 Mouse 0.5-0.7 150 20000 Differentiation
PIM2 PIM2 PIM2 pim-2 oncogene PIM2 Cell Signaling 4730 Rabbit > 0.7 300 20000 Differentiation
peroxisome proliferator-activated receptor PPARG PPARG PPARG PPARγ Santa Cruz sc7273 Mouse > 0.7 150 20000 Differentiation gamma
PRKCA PRKCA PRKCA protein kinase C, alpha PKCα Upstate 05-154 Mouse > 0.7 10000 20000 PKC
PRKCA.pS657 PRKCA-phospho ser657 PRKCA protein kinase C, alpha Activation PKCα-p657(Ser) Upstate 06-822 Rabbit 0.5-0.7 10000 20000 PKC
PRKCB.I PRKCB PRKCB protein kinase C, beta PKCβ I Santa Cruz sc8049 Mouse 0.5-0.7 500 20000 PKC
PRKCD.pS645 PRKCD-phospho Ser645 PRKCD protein kinase C, delta PKCδ-645(Ser) Upstate 07-874 Rabbit > 0.7 400 20000 PKC
PTEN PTEN PTEN phosphatase and tensin homolog PTEN Cell Signaling 9552 Rabbit > 0.7 4000 20000 mTOR
PTK2 PTK2 PTK2 protein tyrosine kinase 2 Fak Cell Signaling 3285 Rabbit > 0.7 1000 20000 Adhesion protein tyrosine phosphatase, non-receptor type PTPN11 PTPN11 PTPN11 SHP-2 Epitomics 1590-1 Rabbit 0.5-0.7 800 20000 STP 11
RB1 RB1 RB1 retinoblastoma 1 Rb BD Pharmingen 554136 Mouse > 0.7 1000 20000 CellCycle
RB1-phospho RB1.pS807_811 RB1 retinoblastoma 1 Inactivation Rb (P-Ser807/811) Cell Signaling 9308 Rabbit > 0.7 1000 20000 CellCycle ser807/811 RPTOR independent companion of mTOR complex RICTOR RICTOR RICTOR Rictor Cell Signaling 2114 Rabbit 0.5-0.7 200 20000 mTOR, RPS6 2 RICTOR Phospho RPTOR independent companion of mTOR complex Stimulates binding RICTOR.pT1135 RICTOR Rictor-P1135(Tyr) Cell Signaling 3806 Rabbit > 0.7 2000 20000 mTOR, RPS6 Thr1135 2 with 14-3-3
RPS6 RPS6 RPS6 ribosomal protein S6 S6 Ribosomal protein Cell Signaling 2217 Rabbit > 0.7 2000 20000 RPS6
S6 Ribosomal RPS6-phospho RPS6.pS235_236 RPS6 ribosomal protein S6 Activation protein(phospho- Cell Signaling 2211 Rabbit > 0.7 2000 20000 RPS6 ser235/236 ser235/236) S6 Ribosomal RPS6-phospho RPS6.pS240_244 RPS6 ribosomal protein S6 Activation protein(phospho- Cell Signaling 2215 Rabbit > 0.7 1000 20000 RPS6 ser240/244 ser240/244)
RPS6KB1 RPS6KB1 RPS6KB1 ribosomal protein S6 kinase, 70kDa, polypeptide 1 p70S6K Cell Signaling 9202 Rabbit > 0.7 250 20000 RPS6
RPS6KB1-phospho RPS6KB1.pT389 RPS6KB1 ribosomal protein S6 kinase, 70kDa, polypeptide 1 Activation p70S6K(p-thr389) Cell Signaling 9205 Rabbit > 0.7 250 20000 RPS6 thr389
RAPTOR RPTOR RPTOR Regulatory associated protein of mTOR complex 1 Raptor Cell Signaling 2280 Rabbit > 0.7 1000 20000 mTOR, RPS6
SFN SFN SFN stratifin X14.3.3Sigma Upstate 05-632 Mouse 500 20000 TP53
SIRT1 SIRT1 SIRT1 sirtuin 1 SIRT1 Abcam ab32441 Rabbit 0.5-0.7 2000 20000 Histone
SMAD1 SMAD1 SMAD1 SMAD family member 1 smad1 Epitomics 1649-1 Rabbit > 0.7 200 20000 SMAD
SMAD2 SMAD2 SMAD2 SMAD family member 2 SMAD2 Cell Signaling 5339 Rabbit > 0.7 10000 20000 SMAD
Smad2-p SMAD2.pS245 SMAD2.p245 SMAD2 SMAD family member 2 Activation Cell Signaling 3104 Rabbit > 0.7 800 20000 SMAD S245/250/255
SMAD2.pS465 SMAD2.pS465 SMAD2 SMAD family member 2 Activation Smad2-p S465/467 Cell Signaling 3108 Rabbit 0.5-0.7 800 20000 SMAD
SMAD3 SMAD3 SMAD3 SMAD family member 3 SMAD3 Cell Signaling 9523 Rabbit > 0.7 800 20000 SMAD
SMAD4 SMAD4 SMAD4 SMAD family member 4 smad4 Santa Cruz sc7966 Mouse > 0.7 400 20000 SMAD
SMAD5 SMAD5 SMAD5 SMAD family member 5 SMAD5 Epitomics 1682-1 Rabbit 0.5-0.7 2000 20000 SMAD
SMAD5.pS463 SMAD5pS463 SMAD5 SMAD family member 5 Activation Smad5-p S463/465 Epitomics 2224-1 Rabbit > 0.7 1000 20000 SMAD
SMAD6 SMAD6 SMAD6 SMAD family member 6 Smad6 Cell Signaling 9519 Rabbit ? 100 20000 SMAD
SOCS2 SOCS2 SOCS2 suppressor of cytokine signaling 2 SOCS2 Abcam ab92847 Rabbit > 0.7 400 20000 STP
spleen focus forming virus (SFFV) proviral SPI1 SPI1 SPI1 PU.1 Cell Signaling 2258 Rabbit 0.5-0.7 5000 20000 Transcription integration oncogene
SPP1 SPP1 SPP1 secreted phosphoprotein 1 Osteopotin Santa Cruz sc-21742 Mouse 0.5-0.7 200 20000 Adhesion
SQSTM1 SQSTM1 SQSTM1 sequestosome 1 P62 Santa Cruz sc-28359 Mouse 0.5-0.7 200 20000 Autophagy
v-src avian sarcoma (Schmidt-Ruppin A-2) viral SRC SRC SRC Src Upstate 05-184 Mouse > 0.7 2000 20000 SRC oncogene homolog v-src avian sarcoma (Schmidt-Ruppin A-2) viral SRC.pY416 SRC-phospho tyr416 SRC Activation Src(phospho-tyr416) Cell Signaling 2101 Rabbit > 0.7 200 20000 SRC oncogene homolog
SSBP2 SSBP2 SSBP2 single-stranded DNA binding protein 2 SSBP2-I(alpha) Private-Nagarajan Rabbit 0.5-0.7 2000 15000 Differentiation
signal transducer and activator of transcription 1, STAT1 STAT1 STAT1 stat1 Cell Signaling 9172 Rabbit > 0.7 400 20000 STAT 91kDa signal transducer and activator of transcription 1, Stat1(phospho- STAT1.pY701 STAT1-phospho tyr701 STAT1 Activation Cell Signaling 9171 Rabbit ? 200 20000 STAT 91kDa tyr701) signal transducer and activator of transcription 3 STAT3 STAT3 STAT3 Stat3 Upstate 06-596 Rabbit 0.5-0.7 200 20000 STAT (acute-phase response factor) signal transducer and activator of transcription 3 STAT3.pS727 STAT3-phospho ser727 STAT3 Activation Stat3-p727(Ser) Cell Signaling 9134 Rabbit 0.5-0.7 400 20000 STAT (acute-phase response factor) signal transducer and activator of transcription 3 STAT3.pY705 STAT3-phospho tyr705 STAT3 Activation Stat3 p705(Tyr) Cell Signaling 9131 Rabbit > 0.7 400 20000 STAT (acute-phase response factor)
STAT5A_B STAT5A/STAT5B STAT5A signal transducer and activator of transcription 5A Stat5 Cell Signaling 9352 Rabbit > 0.7 400 20000 STAT
STAT5A/STAT5B Stat5(phospho- STAT5A_B.pY694 STAT5A signal transducer and activator of transcription 5A Activation Cell Signaling 9351 Rabbit ? 100 20000 STAT phospho Tyr694 Tyr694) signal transducer and activator of transcription 6, Stat6(phospho- STAT6.pY641 STAT6-phospho tyr641 STAT6 Activation Cell Signaling 9361 Rabbit ? 500 20000 STAT interleukin-4 induced tyr641)
STK11 STK11 STK11 serine/threonine kinase 11 LKB1/STK11 Cell Signaling 3050 Rabbit 0.5-0.7 800 20000 Autophagy
STMN1 STMN1 STMN1 stathmin 1 Stathmin Epitomics 1972-1 Rabbit > 0.7 10000 20000 FLI1
TAZ TAZ TAZ Tafazzin Taz Abcam ab3961 Rabbit > 0.7 2000 20000 HIPPO
TAZ.pS89 TAZ Phospho Ser89 TAZ Tafazzin Inactivation Taz-P89(Ser) Santa Cruz sc-17610-R Rabbit ? 300 20000 HIPPO
TCF4 TCF4 TCF4 transcription factor 4 TCF-4 Santa Cruz sc8632 Goat ? 800 20000 Transcription
TGM2 TGM2 TGM2 transglutaminase 2 TG2 Abcam ab2386 Mouse > 0.7 4000 20000 Adhesion
TNK1 TNK1 TNK1 tyrosine kinase, non-receptor, 1 TNK1 Agent AP7722a Rabbit > 0.7 800 20000 MEK
TP53 TP53 TP53 tumor protein p53 TP53 BD Bioscience 554294 Mouse 0.5-0.7 750 20000 ApopReg, TP53
Blocks MDM2 TP53.pS15 TP53-pS15 TP53 tumor protein p53 TP53(phospho Ser 15) Cell Signaling 9284 Rabbit > 0.7 250 20000 ApopReg, TP53 binding NB100- TRIM24 TRIM24 TRIM24 tripartite motif containing 24 TRIM24 Novus Rabbit ? 2000 20000 Histone, TP53, Ubiquitin 2597
TSC2 TSC2 TSC2 tuberous sclerosis 2 TSC2 Epitomic 1613-1 Rabbit > 0.7 800 20000 Autophagy, mTOR
TSC2.pT1462 TSC2 TSC2 tuberous sclerosis 2 Inactivation TSC2 Cell Signaling 3617 Rabbit > 0.7 500 20000 Autophagy, mTOR
VASP VASP VASP vasodilator-stimulated phosphoprotein VASP Cell Signaling 3112 Rabbit ? 300 20000 Hypoxia
von Hippel-Lindau tumor suppressor, E3 ubiquitin VHL VHL VHL VHL Novus NB100-485 Rabbit 0.5-0.7 4000 20000 Hypoxia protein ligase
WEE1 WEE1 WEE1 WEE1 G2 checkpoint kinase Wee 1 Cell Signaling 4936 Rabbit 0.5-0.7 1000 20000 CellCycle
WTAP WTAP WTAP Wilms tumor 1 associated protein WTAP Sanjay Bansal from UTSA Rabbit > 0.7 20000 20000 CellCycle, FLI1, Histone
XPO1 XPO1 XPO1 exportin 1 (CRM1 homolog, yeast) CRM1 Santa Cruz sc-5595 Rabbit > 0.7 3000 20000 Cytoskeletal
YAP1 YAP1 YAP1 Yes-associated protein 1 YAP Cell Signaling 4912 Rabbit 0.5-0.7 300 20000 ApopReg, HIPPO YAP1 phospho Serine YAP1.p YAP1 Yes-associated protein 1 Inactivation YAP-p(ser127) Cell Signaling 4911 Rabbit 0.5-0.7 1000 20000 ApopReg, HIPPO 127
YES1 YES1 YES1 YES proto-oncogene 1 Yes-1 Abcam ab133314 Rabbit > 0.7 5000 20000 HIPPO, SRC
tyrosine 3-monooxygenase/tryptophan 5- YWHAZ YWHAZ YWHAZ monooxygenase activation protein, zeta 14-3-3-zeta Chemicon AB9746 Rabbit > 0.7 1500 20000 TP53 polypeptide Supplementary Table S4. Protein membership for the 31 defined protein functional groups.
Protein Number of Functional Antibodies Antibodies Group CAV1, FN1, IGFBP2, ITGA2, ITGAL, ITGB3, PTK2, Adhesion 9 SPP1, TGM2 BAD, BAK1, BAX, BCL2, BCL2L1, BCL2L11, BID, Apoptosis BH3 8 MCL1 Apoptosis IAP 4 BIRC2, BIRC5, DIABLO, XIAP CASP3, CASP3.cl175, CASP7.cl198, CASP8, Apoptosis 9 CASP9, CASP9.cl315, CASP9.cl330, PARP1, Occurring PARP1.cl214 Apoptosis 4 TP53, TP53.pS15, YAP1, YAP1p Regulating ATF3, BECN1, PARK7, SQSTM1, STK11, TSC2, Autophagy 7 TSC2.pT1462 BRCA2, CCNB1, CCND1, CCND3, CCNE1, CCNE2, CDK1, CDK2, CDK4, CDKN1A, CDKN1B, Cell Cycle 20 CDKN1B.pS10, CDKN2A, FKHRL1, FOXO3A, MYC, RB1, RB1.pS807_811, WEE1, WTAP CREB 4 ATF3, BECN1, CREB1, CREB1.pS133 Cytoskeletal 4 NF2, NF2.pS518, NRP1, XPO1 Differentiation 6 GATA1, GATA3, PIM1, PIM2, PPARG, SSBP2 FLI1 5 FLI1, NCL, NPM1.3542, STMN1, WTAP Heat shock 2 HSPB1, GRP78 BRCA2, NF2, NF2.pS518, TAZ, TAZ.pS89, YAP1, HIPPO 8 YAP1p, YES1 BMI1, CLPP, DDX17, FLI1, H3K4Me2, H3K4Me3, Histone H3K27Me3, HDAC1, HDAC2, HDAC3, HDAC6, 18 modification HIST3H3, HNRNPK, NCL, SIRT1, KDM1A, TRIM24, WTAP Hypoxia 4 HIF1A, KDR, VASP, VHL MAP2K1, MAPK1, MAPK9, MAPK14, MAPK 5 MAPK14.pT180Y182 MEK 6 BRAF, DUSP6, ELK1.pS383, KIT, LYN, TNK1 Metabolic 2 ASNS, ODC1 EGFR, INPP5D, INPPL1, IRS1.pS1101, MTOR, MTOR.pS2448, PDK1, PDK1.pS241, PIK3CA, mTOR 16 PIK3R1_2, PTEN, RICTOR, RICTOR.pT1135, RPTOR, TSC2, TSC2.pT1462 AKT1, AKT1_2_3.pS473, AKT1_2_3.pT308, PI3KAKT 8 ELK1.pS383, FKHRL1, FOXO3A, GAB2, GAB2.pY452 PRKCA, PRKCA.pS657, PRKCB.I, PRKCD.pS645, PKC 5 RELA DDX17, MSI2, RICTOR, RICTOR.pT1135, RPS6, Ribosome 10 RPS6.pS235_236, RPS6.pS240_244, RPS6KB1, RPS6KB1.pT389, RPTOR SMAD1, SMAD2, SMAD2.pS245, SMAD2.pS465, SMAD 9 SMAD3, SMAD4, SMAD5, SMAD5.pS463, SMAD6 SRC 3 SRC, SRC.pY416, YES1 MAPK9, STAT1, STAT1.pY701, STAT3, STAT 9 STAT3.pS727, STAT3.pY705, STAT5A_B, STAT5A_B.pY694, STAT6.pY641 EGFR, ERBB2, ERBB2.pY1248, IGF1R, KIT, LYN, STP Upstream 9 MET.pY1230_1234_1235, PTPN11, SOCS2 T-cell 5 CD74, LCK, LGALS3, NOTCH1.cl1744, NOTCH3 IRS1.pS1101, MDM2, MDM4, SFN, TP53, TP53 8 TP53.pS15, TRIM24, YWHAZ DDX17, DLX1, EIF2AK2, EIF2AK2.pS51, Transcription 15 EIF2AK2.pT451, EIF2S1, EIF4E, GATA1, GATA3, JUN.pS73, JUNB, MYC, NR4A1, SPI1, TCF4 Ubiquitin 4 CBL, ERN1, GRP78, TRIM24 Wnt signaling 3 CTNNA1, CTNNB1, LEF1 Supplementary Table S5. AML protein constellation membership for the 136 protein clusters.
Constellation Protein cluster 3 SMADC4
1 ApopOccurC1 3 TcellC2 1 FLI1C3 3 TP53C5 1 IAPC3 3 UbiquitinC1 1 MTORC2 3 WNTC2 1 PKCC1 4 AdhesionC2
1 RibosomeC1 4 AutophagyC5
1 SRCC2 4 BH3C3
1 UbiquitinC4 4 BH3C4
2 AutophagyC1 4 DifferentiationC4 2 CytoskeletalC2 4 DifferentiationC5 2 MEKC3 4 HeatshockC2 2 PI3KAKTC1 4 HistoneC4 2 STATC1 4 HypoxiaC4 2 STPC4 4 MAPKC2 2 TranscriptionC1 4 MEKC4 3 AdhesionC1 4 MetabolicC4 3 ApopRegC5 4 PKCC5 3 AutophagyC4 4 SMADC5 3 BH3C5 4 STATC2 3 CREBC5 4 STPC2 3 CytoskeletalC1 4 TcellC4 3 DifferentiationC1 4 TP53C2 3 FLI1C4 5 AdhesionC4 3 HeatshockC1 5 ApopRegC3 3 HIPPOC2 5 CellCycleC1 3 HistoneC3 5 HIPPOC3 3 HistoneC5 5 MAPKC1 3 HypoxiaC3 5 TP53C1
3 IAPC4 5 TranscriptionC2
3 MAPKC3 5 WNTC3
3 MetabolicC3 6 AdhesionC3
3 MTORC4 6 ApopRegC1
3 PKCC2 6 AutophagyC2
3 RibosomeC4 6 CellCycleC2
6 HIPPOC1 8 MetabolicC5 6 HypoxiaC2 8 RibosomeC2 6 MEKC2 8 TP53C4
6 PI3KAKTC4 8 TP53C6
6 PI3KAKTC5 8 TranscriptionC4
6 SMADC1 8 UbiquitinC3
6 TranscriptionC3 9 CellCycleC4
6 WNTC4 9 PI3KAKTC2
7 ApopOccurC2 9 PI3KAKTC3 7 ApopOccurC3 9 SMADC2 7 AutophagyC3 10 CREBC1 7 BH3C1 10 CytoskeletalC3 7 CREBC4 10 HistoneC2 7 DifferentiationC2 10 STATC3 7 FLI1C2 11 BH3C2 7 HeatshockC3 11 CREBC2 7 HeatshockC5 11 DifferentiationC3 7 IAPC2 11 FLI1C5 7 MAPKC4 11 PKCC3 7 MAPKC5 11 SMADC3 7 MetabolicC1 11 STPC3 7 MTORC3 11 TP53C3 7 PKCC4 12 FLI1C1 7 RibosomeC3 12 HistoneC1 7 RibosomeC5 12 HypoxiaC1 7 SRCC1 12 IAPC1 7 STPC1 12 MEKC1 7 TcellC3 12 MetabolicC2 7 WNTC1 12 MTORC1 8 ApopRegC2 12 SRCC3 8 ApopRegC4 12 TcellC1 8 CellCycleC3 12 UbiquitinC2 8 CREBC3 8 HeatshockC4 8 HIPPOC4
Supplementary Table S6. (A) This table shows are the variables considered in the Univariate Cox Proportional Hazard Model. Only variables that had sufficient data available were considered in the model. Similar to what has traditionally been done with cytogenetics, we lumped our 8 signatures together into signatures that had a favorable (signature 2, 4), an intermediate (signature 1, 3, and 6), or an unfavorable (signature 5, 7) outcome. Variables that were significant in the univariate model were then included in the multivariate analysis (B). Backward elimination of the most non- significant variables first, resulted in the best predictive model, incorporating the unfavorable protein signatures and the favorable cytogenetics. A
beta 95% CI for HR Wald test P-value
Favorable Signatures -0.78 0.46 (0.14-1.5) 1.7 0.19
Intermediate Signatures -0.51 0.6 (0.34-1.1) 3 0.084
Unfavorable Signatures 0.79 2.2 (1.2-3.9) 7.3 0.0068
Age 0.011 1 (0.96-1.1) 0.16 0.69
Favorable Cytogenetics -1.2 0.3 (0.12-0.75) 6.6 0.01
Intermediate Cytogenetics 0.91 2.5 (1.2-5.3) 5.4 0.02
Unfavorable Cytogenetics 0.25 1.3 (0.4-4.1) 0.17 0.68
White blood cell count -2.70E-05 1 (1-1) 0.26 0.61
Absolute blast count PB 1.40E-06 1 (1-1) 0.29 0.59
Hemoglobin -0.024 0.98 (0.87-1.1) 0.15 0.7
Platelet -0.0017 1 (0.99-1) 0.44 0.51
B
coef exp(coef) se(coef) Z-score P-value
Unfavorable Signatures 0.638 1.839 0.299 2.13 0.033
Favorable Cytogenetics -1.153 0.316 0.476 -2.42 0.015
Supplementary Table S7. The combined ALL and AML protein constellation membership for the 142 protein clusters.
Constellation Protein cluster 4 TranscriptionC4
1 DifferentiationC3 4 UbiquitinC3 1 FLI1C2 5 AdhesioC3 1 HistoneC5 5 ApopRegC1 1 TcellC4 5 CellCycleC2 1 TP53C6 5 CREBC5 1 TranscriptionC3 5 CytoskeletalC1 1 UbiquitinC5 5 FLI1C1 2 AutophagyC5 5 HeatshockC3 2 HypoxiaC1 5 HIPPOC1 2 MEKC4 5 IAPC2 2 MTORC2 5 SMADC2
2 STPC3 6 AdhesionC2
2 WNTC4 6 ApopOccurC1
3 ApopOccurC3 6 CellCycleC3 3 BH3C2 6 CytoskeletalC2 3 CREBC2 6 HIPPOC3 3 HeatshockC4 6 HypoxiaX2 3 IAPC3 6 MTORC1 3 MAPKC1 6 SRCC1 3 MetabolicC1 6 STATC1 3 MetabolicC4 7 BH3C1 3 PI3KAKTC1 7 CREBC1 3 PKCC1 7 HeatshockC2 3 PKCC2 7 HistoneC1 3 RibosomeC1 7 MTORC3 3 RibosomeC3 7 UbiquitinC6 3 SRCC4 7 WNTC2 3 STATC2 8 ApopOcurC2 4 BH3C4 8 ApopRegC3 4 DifferentiationC2 8 AutophagyC2 4 HistoneC2 8 BH3C5 4 PI3KAKTC4 8 FLI1C3 4 SMADC1 8 IAPC1 4 TcellC5 8 MAPKC4 4 TP53C1 8 MEKC1 8 MEKC3 10 TranscriptionC2 8 MetabolicC2 11 ApopRegC5 8 MetabolicC3 11 AutophagyC4
8 PKCC4 11 CREBC3
8 PKCC5 11 CytoskeletalC3
8 RibosomeC2 11 HeatshockC1
8 RibosomeC4 11 HIPPOC4
8 SRCC3 11 HypoxiaX4
8 STATC3 11 IAPC4
8 STPC1 11 MAPKC3
8 STPC2 11 MTORC4
8 TcellC1 11 RibosomeC5
8 TP53C2 11 SMADC5
8 UbiquitinC2 11 STPC5
9 ApopRegC2 11 TP53C4 9 AutophagyC3 11 UbiquitinC1 9 DifferentiationC5 12 AdhesionC1 9 DifferentiationC6 12 AdhesionC4 9 HypoxiaC3 12 ApopRegC4 9 MAPKC2 12 AutophagyC1 9 MEKC2 12 BH3C3 9 PI3KAKTC3 12 CREBC4 9 PKCC3 12 FLI1C4 9 SMADC4 12 FLI1C5 9 STPC4 12 HeatshockC5 9 TcellC3 12 HistoneC3 9 TP53C5 12 HistoneC4 9 TranscriptionC5 12 MetabolicC5 9 WNTC3 12 SRCC2 10 CellCycleC1 12 TcellC2 10 DifferentiationC1 12 TP53C3 10 DifferentiationC4 12 TranscriptioC1 10 HIPPOC2 12 UbiquitinC4 10 PI3KAKTC2 12 UbiquitinC7
10 PI3KAKTC5 12 WNTC1
10 SMADC3
Supplementary Table S8. Protein cluster membership for the leukemic cell lines. − 3 − 3 − 3 3 3 − 2 1 3 − − 3 − 3 − 3 3 3 3 3 3 3 − − WNT − − − − − − 2 3 3 3 1 1 3 − − − − − − − − − − 2 2 − 2 2 − − 1 1 1 − − 2 − − − − 1 1 − 2 Ubiquitin − − − − 2 − − 3 3 2 − 3 1 − − − − − 1 1 1 1 1 − 1 1 1 1 1 − − 1 1 1 − 1 1 1 1 1 1 1 − − Transcription 1 1 1 − 1 1 1 1 − 1 1 1 1 − − − − − − − − − − − − − − − − − − − − − − − − − − − − − − − TP53 − − − − − − − − − − − − − − − − − − 1 − 1 − − − − 1 − − 4 − − − − 1 1 4 − − − 1,4 1,4 1,4 1,4 3,4 3,4 1,4 1,4 3,4 1,4 1,4 1,4 1,4 1,4 1,4 1,4 1,4 TCELL 2,4 1,4 1,4 1,4 1,4 − − 1 − − − − − − − − 2 − 1 − 1 1 − − − − 2 − − − − 1 STAT 1 − − 1 − − − 1 1 1 1 − 1 − 1 1 − − − − − − − − − − − − 1 − − − − − − − − 2 1 2 − − − − SRC − − − − − − − − − − − − − − − 2 − − 3 3 − 1 5 5 5 − 5 3 − 5 − 1 5 5 5 5 5 5 1 1 3 3 3 − − 5 5 1 − − − 5 − − 1,3 1,3 1,3 1,3 SMAD 1,3 1,3 1,3 − − − − − − − − − − − − − − 4 − − − − − − − − 2 − − − RPS6 − − 4 − − − − − − − − − − − − − − − − − − − 5 − − − − − 5 − − − − − − − − − − − − − − − PKC − − − − − − − 5 − − − 5 − − − − − − − 5 − − 5 5 5 5 − − − − 5 − − − 5 − 5 5 5 − − − − − PI3KAKT − − − 4 − − − − − 5 − 5 − − − − − − − − 1 1 1 − − − − mTOR − − − − − 1 1 − 1 − − − − − − − − − − − − − − − 1 − 1 − 1 − − − − − − 3 3 3 3 3 − − 3 1 − − − 3 − 3 3 3 3 3 3 3 − 3 − − − − − 1 − − − − − − − 3 1 − − − 3 Metabolic 3 3 3 − − − 3 3 3 − − 3 3 3 3 − − 3 3 3 3 3 3 − − 3 − 3 − − 3 − 3 3 3 3 − − 3 3 1 − 3 3 MEK − − 1 − 1 1 1 1 − − − − − 3 3 − − 1 − 1 − 3 1 1 1 − − − 4 1 − − − − − − 4 1 − − − − 1 −
MAPK 1,4 4 1 1 1 − − 2 1 1 1 − − − 4 1 − 2 2 − − − 1 − 1 − 2 − 2 1 1 4 1 1,2 1,2 1,2 1,2 Hypoxia 1,2 1,2 1,2 1,2 1,2 1,2 1,2,4 1,2,4 − − − − − − − − − − − − − − − 4 − − − − − − − − − − − − − − − − − − − − − − − − − − −
Histone 1,2 − − 1 2 2 − − − − − − − − − − − − − − − − − − − − − − 1 − − − − − − − − − − − − − − −
HIPPO 1,2 − − 1 − − − 1 − − − − − − − − 1 − − − − − − − − − − − − − − − − − − − 1 1 − − 1 − − − Heatshock − − − 2 2 2 − 2 3 − − − − − − − 2 − − − − − − 2 − − − − − − 1 2 − − − 2 1 − − − − − − − FLI1 − − − − − − − − − − − 3 3 − 3 − − 4 − − − 4 3 − − − − − 3 4 − − − − − − 3 3 − − − 1 3 − Differentiation 3 − − − − − − − − − − − − − − − − − − − − − − − − − − − − − − − − 1 − 1 − − − − − − − − Cytoskeletal − − − − 1 − − − − 3 3 2 − 1 − − 4 4 4 4 − 2 1 − − 3 − − − 3 3 1 − − − 1 1 − − 2 − − 1,3 1,3 CREB 1,2 − − − − − − − − − − − − − − − − − − − − − − − − − − − − − − − − − − − − − − − − − − − CellCycle − − − 1 1 1 − − − − 1 3 − − − − 3 3 1 1 3 3 − 3 3 3 − 1 − 3 1 − 1 1,3 2,3 2,3 1,3 1,3 Autophagy 1,3 1,3 1,3 2,3 1,3 1,3 2,3 3 − 2 2 2 2 2 − 2 1,3 1,3 2,3 1,3 2,3 1,3 2,3 1,3 1,3 1,3 1,3 1,3 1,3 2,3 1,3 1,3 1,3 2,3 1,3 1,3 1,3 1,3 2,3 2,3 1,3 1,3 1,3 2,3 1,3 1,3 1,3 IAP 1,3 1,2,3 1,2,3 1,3,4 − 4 − − 4 − − − 4 − − − − 5 − − − − 4 − − − − − − − − − − − − − − 2 4 − 5 − − 4 −
BH3 2,4 1,2 1,2,4 − − 2 2 − − − − − − − − − − − − − − 2 2 1 − − − − − − − − − − − − − − − − − − − − − − ApopReg − 1 − − − − − − − 1 − − − − − 3 − 1 − − − − 3 − 1 − 1 − 3 − − − − − − − − − 1 − 3 3 3 − ApopOccur − − − − − − − − − − − − − − − − − − − − − − − − − − − − − − − − − − − − Adhesion − − − − − − − − − 92 94 92 98 98 93 Viability 96 91 93.8 93.6 95.5 95.9 95.1 96.6 97.2 94.1 94.5 95.1 98.4 95.7 96.5 98.7 93.3 94.6 95.4 98.1 98.6 97.9 96.9 96.4 92.5 94.4 96.9 94.3 97.8 98.8 97.5 99.7 96.9 97.2 99.1 95.6 96.6 96.4 8 3 2 3 3 7 2 2 7 7 5 5 5 2 1 1 1 1 3 3 2 2 2 2 5 5 4 6 6 2 2 12 15 16 15 13 13 12 12 10 14 16 Box 14 16
Age Adult Pediatric Adult Adult Adult Adult Pediatric Pediatric Adult Adult Adult Adult Adult Pediatric (20y.) Pediatric (20y.) Pediatric (20y.) Pediatric (20y.) Pediatric (20y.) Pediatric (20y.) Adult Adult Adult Adult Pediatric Pediatric Pediatric Adult Adult Pediatric Pediatric Pediatric Adult Adult Adult Adult Adult Adult Adult Pediatric Pediatric Adult Adult Adult Adult
Disease AML M7 MDS Mantle Cell Lymphoma AML M3 AML M3 AML M4 AML M5a AML M5a AML M5a AML M5a AML M5a AML M5a AML, M0 T-ALL T-ALL T-ALL T-ALL CML CML AML M2 AML M2 AML M5 CML CML T315I CML T315I CML T315I CML AML M3 AML M3 AML M3 T-ALL B-ALL Pre-B ALL Pre-B ALL T-ALL Burkitt's lymphoma B-cells B-cells AML M2 AML M2 AML M2 AML M2 AML M2 lymphoma
Mycoplasma neg neg 2nd-neg neg neg 2nd-neg neg neg neg neg neg neg neg neg neg neg neg neg neg neg neg neg 2nd-neg neg neg neg neg neg neg 2nd-neg neg neg neg neg neg neg neg neg neg neg neg neg
Cell line Molm13 Molm13 P53 K/D Molm13 P53 vector Molm14 Molm14 Molm14 treated Molm16 Molt3 KG-1 treated KOPTI-K1 (lable:KOPTI) (Teresa label: KOPTI ALL) M-07e MDSL MINO ML-1 ML-1 treated ML-2 (AML-ML2) Kasumi-1 treated KBM3 KBM5 KBM5 STI treated, w/o STI KBM5 STI, w/o STI KBM5 STI, w/STI KBM5 treated KG-1 KG-1 HL-60 treated JeKo-1 Jurkat Jurkat I9.2 Caspase8 mut Jurkat treated K562 K562 treated Kasumi-1 CCRF-CEM Daudi GM00131 GM00131 treated HL-60 HL-60 HL-60 TRE TGM2 HL-60 TRE TGM2 control Blin-1 BV173 BV173 treated Molt4 neg T-ALL Pediatric 3 94.8 − − − − 2 1 − 2 − − − − − − 1 3 − − − − 5 − 3 − 1 − − 1 1 − MR2 treated neg AML, M3 16 93.1 − − − 2 1,3 3 − − − − 2 − − − − 1 3 1 1 − 5 − 5 − 1 1 − 1 3 3 MV4-11 neg AML M5 Pediatric 6 93 − 3 − − 1,3 2,3 − 1 − − 1,2 − − − 2,4 − − 3 − − − − 5 − − 4 − 1 − 3 MV4-11 IDH1 R132H neg AML M5 Pediatric 13 91 − 1,3 2 2,4 1,3 2,3 − 1 − − 2 − − − 1 − 3 − 1 5 − − 5 − − 1,4 4 1 1 3 MV4-11 IDH1 wt(vector) neg AML M5 Pediatric 11 91.1 − 1,3 2 2,4 2,3 2,3 − 1,4 − − 2 − − − 1,2 1 3 3 − − − − 5 − 1 1,4 − 1 − 3 MV4-11 treated AML M5 Pediatric 6 91 − − − 1 2 − − − − − − − − − 1 − 3 3 − − − − 5 − 1 1 − 1 − 3 Nalm6 treated neg Pre-B ALL Pediatric 8 98.5 − − − − 1,3 − − − − 3 − − − − 1,2 1 3 − − − − − − − 1 2,4 − 1 − − NB4 neg AML M3 Adult 3 94 − 3 − − 2,3 − − − − − − − − − − 1 3 3 1 5 − − 5 − 2 1,4 − 1 − 3 OCIAML2 neg AML M4 Adult 14 96.2 − − − − 2,3 3 − 1 − − 2 − − − 1,2 5 3 3 − − − − 5 − − 1,4 − 1 3 − OCIAML3 neg AML M4 Adult 6 93.6 − 1 2 − 1,3 3 − − − 4 2,3 − − − 1 1 − 3 − 5 − − − − − 1,4 − 1 − − OCIAML3 550 TGM2-overexp neg AML M4 Adult 8 97 − − − − 2,3 − − − − − 2 − − − 4 − − 3 − 4 − − − − − 4 − 1 − − OCIAML3 708 ppp2R2A shRNAneg AML M4 Adult 13 95.4 − − − 4 1,2,3 3 − 3 − − 2 − − − 1,2 1,4 − 3 − − − − 5 − − 1,4 − 1 3 3 OCIAML3 709 ppp2R2A shRNAneg AML M4 Adult 12 99 − − − − 1,3 3 − 1,3 − − 2 − − − 1,2 1 − 3 − − 1 − − − 1 4 − 1 2 3 OCIAML3 Bcl2 overexpression neg AML M4 Adult 5 94.3 − 1 − 4 2,3 − − 1,3 − − − − − − 1 1,4 − 3 − − 1 − 5 2 1,2 1,4 − 1 − 3 OCIAML3 Bcl2 vector neg AML M4 Adult 5 93.9 − − − − 3 − − − − 4 1 − − − 1,2 4 − 3 − − 1 − 5 1,2 − 1,4 − 1 − 3 OCIAML3 IDH1 R132H neg AML M4 Adult 9 98.5 − − − − 1,3 3 − 3 − − 2 − − − 1,2 1 − 3 − − − − − − 2 1,4 − 1 2 − OCIAML3 IDH1 wt(vector) neg AML M4 Adult 11 94.5 − − − − 1,2,3 − − − − − 2 − − − 1,2 1 3 3 − − − − − − 1 1,4 − 1 2 − OCIAML3 induxible HIF1a ODD mutneg AML M4 Adult 11? 99 − − − − 3 3 − 1,3 − − 2 − − − 4 1 − 3 − − − − − − − 1,4 − 1 2 − OCIAML3 ITD treated neg AML M4 Adult 15 95.3 − − − − 1 − − 1 − 4 − − 4 − 1,4 1,2 − 3 − − − − − − 1 1,4 − 1 2 3 OCIAML3 ITD vec neg AML M4 Adult 3 92 − − − − 2,3 − − 1 − 4 2 2 − − 1 5 − − − 5 − − − − − 1,4 − 1 − 3 OCIAML3 NS for ppp2R2A shRNAneg AML M4 Adult 13 97.3 − 1 − − 1,3 3 − 1,3 − − 2 1 − − 1,2 1 − 3 − − − − − − − 1,4 − 1 2 − OCIAML3 p100SSAA neg AML M4 Adult 10 96.9 − 1 − − 1,3 3 − 1 − − 2 − − − 1,2 1 − 3 − 5 − − − − − 1,4 − 1 − 3 OCIAML3 P53 shRNA neg AML M4 Adult 1 98.2 − − − − 2,3 − − − − 4 − − − − 1 4 − 3 − − − − − − − 3,4 − 1 − − OCIAML3 P53 vector neg AML M4 Adult 4 97 − − − − 1,3 − − − − − − 2 1 − 4 − − 3 − − − − − − − 1,4 − 1 − − OCIAML3 PI3K active pool #1 neg AML M4 Adult 9 97.5 − − − − 1,2,3 3 3 3 − − 2 − − − 1,2 1 − 3 − 4 − − 5 − 1 4 − 1 2 − OCIAML3 PI3K wt pool#2 1A neg AML M4 Adult 9 99.1 − − − − 1,3 3 − 3 − − 2 − − − 1,2 1,4 − 3 − − − − − − − 1,4 − 1 2 − OCIAML3 Stat5A neg AML M4 Adult 9 97.5 − − − − 1,3 − − 3 − − 2,3 2 − − 1,2 1 − − − − − − − − 1 2 − 1 2 3 OCIAML3 stat5A N642H neg AML M4 Adult 10 96.4 − − 2 − 1,3 − − 1,3 − − 2 1 − − 1,2 1 − 3 − − 1 − − − 1 4 − 1 2 − OCIAML3 stat5A N642H H4F neg AML M4 Adult 10 96.3 − − − − 1,3 3 − 1,3 − − 2 1 − − 1,2 − − 3 − − − − 5 − − 1,3,4 − 1 − 3 OCIAML3 stat5A wt neg AML M4 Adult 9 98.9 − − − − 1,3 − − 3 − − 2 1 − − 1,2 1,4 − 3 − − − − − − 2 1,3,4 − 1 2 − OCIAML3 TRE TGM2 neg AML M4 Adult 12 97.8 − 1 − − 1,2,3 3 − 1,3 − − 2 − − − 4 − 3 3 − − − − − − − 1,4 − 1 2 3 OCIAML3 TRE TGM2 control neg AML M4 Adult 11 99 − − − − 3 3 − 3 − − − − − − 4 1 − 3 − − − − − − − 1,4 − 1 2 3 OCIAML5 neg AML M4 Adult 9 98.1 − − − − 2 3 − 1,3 − − − − − − 1,2 4 − − − − − − 1,3 − − 4 − 1 − − P12 ichikawa neg T-ALL Pediatric 15 98.4 − − − − 1,3 1 − 1 − − − − − − 1,2 − − − − − − − 3 − − − − − 2 − Raji neg Burkitt's lymphoma Pediatric 1 98.7 − − − − 1,4 − − 1 − − − − − − − − − 3 − − − − 5 3 − 2,4 − 1 − − Raji treated neg Burkitt's lymphoma Pediatric 1 95.1 − − − − 1 − − 3 − − − − − − − − 3 3 − − − − − 3 − − − 1 − 3 Ramos neg Burkitt's lymphoma Pediatric 7 94.8 − − − 5 − − − 1 − − − − 1 4 − − 3 − − − 5 − 3 − − − − 1 − − REH neg ALL (non-T; non-B) Pediatric 8 98.2 − − − − 1,3 − − 1,2 − 3 − − 1 − − − − − − 5 − − 3 − 1 1,4 − 1 2 − REH PLKO CTGF neg ALL (non-T; non-B) Pediatric 9 97 − − − − 2,3 − − 2 − 3 − 2 − − − − − 3 − − − 4 3 − 1 − − 1 2 − REH PLKO-NS-shRNA(control) neg ALL (non-T; non-B) Pediatric 4 98 − − − − 1,3 − − 1,2 − 3 − − − − − − − − − − − − 3 − 1 1,4 − 1 2 − REH treated neg ALL (non-T; non-B) Pediatric 8 99.1 − − − − 1,2,3 − − 2 − 3 − − − − − − − − − 5 − − 3 − 1 1 − 1 − − RPMI8226 Myeloma Adult 8 91.7 − 3 − − 1,3 − − 4 − 3 3 − 1,2 − − − − − − 5 − − 3 − − − − 1 − − RS4:11 2nd-negPre-B ALL Adult 15 97.6 − − − − 1,3 1,3 − 3 − 3 − − − − 1,2 − − − − 5 − − 1 − − 3,4 − 1 2 − RS4:11 Treated neg Pre-B ALL Adult 18 94.9 − − − − 1,3 1 − 2 − − − − − − − 4 3 3 − 5 − − 3 − 1 1,4 − 1 − − SKM1 neg AML M5 14 93.5 − − − − 2,3 2,3 − 1 − − − − − − 2 − − 3 − − 5 − 1,3 1,3 1 4 − 1 − − SR neg Large cell immunoblastic lymphoma Pediatric 14 90 − 3 2 − 1,3 2,3 − 3 − − − − − − − − 3 − 1 − − − − 2 − 1,4 − − 1 3 TALL-1 neg T-ALL Adult 16 96.3 − − − − 2,3 1 − − − − − − − − − − − 2 − − − − − − 1 − − − − − TF-1 neg AML M6 Adult 14 92.7 − 3 − − 2 − − − − − − − − − 1 − − 3 − − − − 5 − 1 1 − − 1 − THP-1 neg AML M5 Pediatric 12 95.1 − − − − 1,3 3 − 1 − − 2 − − − − − − 3 − 5 5 − − − − 1,4 − 1 3 − U937 neg AML M5 Adult 1 92.5 − 3 − − 3 3 − − − − − − − − 1,2 − 3 1 − − − − 5 − − 1,4 − 1 − 3 U937 treated neg AML M5 Adult 1 95.8 − − − − 1 − − 3 − 3 − − − − 1 − − − − − − − 5 3 − − − 1 − 3 Supplemental Figures
A B
Co-occurrence Probability Matrix ‘Hypoxia’, K=4
Y1 Y2 Y3 Y4 Y5 Y6 Y7 Y8 Y9 Y10 Y11 Y12 Y13 Y14 Y15 Y16 Y17 Y18 Y19 Y20 Y21 Y22 Y23 Y24 Y25 Y26 Y27 Y28 Y29 Y30 Y31 Y32 Y33 Y34 Y35 Y36 Y37 Y38 Y39 Y40 Y1 0.6 0.8 0.7 0.6 0.6 0.6 0.7 0.7 0.7 0.1 0.1 0.0 0.1 0.1 0.1 0.1 0.1 0.1 0.1 0.1 0.2 0.2 0.2 0.1 0.2 0.1 0.2 0.2 0.1 0.2 0.2 0.2 0.2 0.2 0.2 0.2 0.2 0.2 0.3 Y2 0.6 0.7 0.7 0.6 0.6 0.6 0.6 0.7 0.7 0.0 0.1 0.1 0.1 0.1 0.1 0.1 0.1 0.1 0.1 0.1 0.2 0.2 0.2 0.2 0.2 0.1 0.2 0.2 0.1 0.2 0.2 0.2 0.2 0.2 0.2 0.2 0.2 0.2 0.2 Y3 0.8 0.7 0.7 0.7 0.6 0.7 0.7 0.7 0.7 0.0 0.1 0.1 0.1 0.1 0.1 0.1 0.1 0.1 0.1 0.1 0.1 0.2 0.2 0.1 0.2 0.1 0.1 0.1 0.1 0.2 0.2 0.2 0.2 0.2 0.2 0.2 0.2 0.2 0.3 0.7 0.1 0.2 0.2 Y4 0.7 0.7 0.7 0.6 0.6 0.7 0.7 0.7 0.7 0.1 0.1 0.1 0.1 0.1 0.1 0.1 0.1 0.1 0.1 0.1 0.2 0.2 0.2 0.2 0.2 0.2 0.2 0.2 0.1 0.1 0.2 0.2 0.2 0.2 0.2 0.2 0.2 0.2 0.2 Y5 0.6 0.6 0.7 0.6 0.6 0.7 0.7 0.6 0.6 0.1 0.1 0.1 0.1 0.1 0.1 0.0 0.1 0.1 0.1 0.1 0.1 0.2 0.2 0.1 0.2 0.1 0.2 0.1 0.1 0.2 0.2 0.2 0.2 0.2 0.2 0.2 0.2 0.2 0.2 Y6 0.6 0.6 0.6 0.6 0.6 0.6 0.6 0.6 0.6 0.1 0.1 0.1 0.1 0.1 0.1 0.1 0.1 0.1 0.1 0.1 0.1 0.1 0.1 0.1 0.2 0.2 0.2 0.1 0.1 0.2 0.3 0.2 0.2 0.3 0.3 0.3 0.2 0.2 0.2 C1 Y7 0.6 0.6 0.7 0.7 0.7 0.6 0.6 0.6 0.6 0.0 0.1 0.1 0.1 0.1 0.1 0.1 0.1 0.1 0.1 0.1 0.1 0.2 0.2 0.1 0.3 0.2 0.2 0.1 0.2 0.2 0.2 0.2 0.2 0.2 0.2 0.2 0.2 0.2 0.3 Y8 0.7 0.6 0.7 0.7 0.7 0.6 0.6 0.7 0.7 0.1 0.1 0.1 0.1 0.1 0.1 0.1 0.1 0.0 0.1 0.2 0.2 0.2 0.2 0.1 0.2 0.1 0.2 0.2 0.1 0.2 0.2 0.2 0.2 0.2 0.2 0.3 0.2 0.2 0.2 0.1 0.7 0.1 0.1 Y9 0.7 0.7 0.7 0.7 0.6 0.6 0.6 0.7 0.7 0.1 0.1 0.1 0.1 0.1 0.1 0.1 0.1 0.1 0.1 0.1 0.1 0.2 0.1 0.1 0.1 0.1 0.1 0.2 0.1 0.1 0.2 0.2 0.2 0.2 0.2 0.2 0.2 0.2 0.3 Y10 0.7 0.7 0.7 0.7 0.6 0.6 0.6 0.7 0.7 0.0 0.1 0.1 0.1 0.1 0.1 0.1 0.1 0.1 0.1 0.1 0.2 0.2 0.2 0.2 0.2 0.2 0.2 0.2 0.1 0.1 0.2 0.2 0.2 0.2 0.2 0.2 0.2 0.1 0.2 Y11 0.1 0.0 0.0 0.1 0.1 0.1 0.0 0.1 0.1 0.0 0.6 0.7 0.7 0.7 0.7 0.7 0.8 0.7 0.7 0.2 0.1 0.2 0.2 0.1 0.2 0.1 0.2 0.1 0.1 0.1 0.1 0.1 0.1 0.1 0.1 0.1 0.1 0.1 0.1 Y12 0.1 0.1 0.1 0.1 0.1 0.1 0.1 0.1 0.1 0.1 0.6 0.6 0.6 0.5 0.6 0.5 0.6 0.6 0.5 0.2 0.1 0.1 0.2 0.2 0.2 0.2 0.1 0.1 0.2 0.1 0.1 0.1 0.2 0.1 0.1 0.1 0.2 0.1 0.2 Y13 0.0 0.1 0.1 0.1 0.1 0.1 0.1 0.1 0.1 0.1 0.7 0.6 0.7 0.6 0.7 0.7 0.7 0.7 0.6 0.1 0.1 0.2 0.1 0.2 0.2 0.1 0.1 0.1 0.1 0.1 0.1 0.1 0.1 0.1 0.1 0.1 0.1 0.1 0.1 Y14 0.1 0.1 0.1 0.1 0.1 0.1 0.1 0.1 0.1 0.1 0.7 0.6 0.7 0.6 0.7 0.7 0.7 0.6 0.7 0.1 0.1 0.2 0.1 0.1 0.1 0.1 0.2 0.1 0.1 0.1 0.1 0.1 0.1 0.1 0.1 0.1 0.1 0.1 0.1 0.2 0.1 0.6 0.1 Y15 0.1 0.1 0.1 0.1 0.1 0.1 0.1 0.1 0.1 0.1 0.7 0.5 0.6 0.6 0.7 0.6 0.7 0.6 0.6 0.1 0.1 0.1 0.1 0.1 0.1 0.1 0.1 0.1 0.1 0.2 0.2 0.2 0.2 0.1 0.2 0.2 0.3 0.2 0.2 Y16 0.1 0.1 0.1 0.1 0.1 0.1 0.1 0.1 0.1 0.1 0.7 0.6 0.7 0.7 0.7 0.6 0.7 0.7 0.7 0.1 0.1 0.1 0.1 0.1 0.1 0.1 0.2 0.1 0.1 0.1 0.1 0.1 0.1 0.1 0.1 0.1 0.2 0.1 0.2 C2 Y17 0.1 0.1 0.1 0.1 0.0 0.1 0.1 0.1 0.1 0.1 0.7 0.5 0.7 0.7 0.6 0.6 0.7 0.6 0.7 0.2 0.1 0.2 0.2 0.2 0.1 0.1 0.1 0.1 0.1 0.1 0.1 0.1 0.1 0.1 0.1 0.1 0.1 0.1 0.1 Y18 0.1 0.1 0.1 0.1 0.1 0.1 0.1 0.1 0.1 0.1 0.8 0.6 0.7 0.7 0.7 0.7 0.7 0.7 0.7 0.1 0.1 0.1 0.1 0.1 0.1 0.1 0.2 0.1 0.1 0.1 0.1 0.1 0.1 0.1 0.1 0.2 0.1 0.1 0.1 Y19 0.1 0.1 0.1 0.1 0.1 0.1 0.1 0.0 0.1 0.1 0.7 0.6 0.7 0.6 0.6 0.7 0.6 0.7 0.6 0.1 0.1 0.1 0.1 0.1 0.1 0.1 0.2 0.1 0.1 0.1 0.1 0.1 0.1 0.1 0.1 0.1 0.1 0.1 0.1 0.2 0.1 0.1 0.7 Y20 0.1 0.1 0.1 0.1 0.1 0.1 0.1 0.1 0.1 0.1 0.7 0.5 0.6 0.7 0.6 0.7 0.7 0.7 0.6 0.1 0.1 0.2 0.2 0.2 0.1 0.1 0.1 0.1 0.1 0.2 0.2 0.1 0.1 0.1 0.1 0.2 0.1 0.1 0.2 Y21 0.1 0.1 0.1 0.1 0.1 0.1 0.1 0.2 0.1 0.1 0.2 0.2 0.1 0.1 0.1 0.1 0.2 0.1 0.1 0.1 0.6 0.6 0.6 0.7 0.5 0.6 0.5 0.6 0.7 0.1 0.1 0.1 0.1 0.1 0.1 0.1 0.1 0.1 0.1 Y22 0.2 0.2 0.1 0.2 0.1 0.1 0.1 0.2 0.1 0.2 0.1 0.1 0.1 0.1 0.1 0.1 0.1 0.1 0.1 0.1 0.6 0.5 0.6 0.7 0.6 0.6 0.6 0.6 0.7 0.2 0.1 0.1 0.1 0.1 0.1 0.1 0.1 0.1 0.1 Y23 0.2 0.2 0.2 0.2 0.2 0.1 0.2 0.2 0.2 0.2 0.2 0.1 0.2 0.2 0.1 0.1 0.2 0.1 0.1 0.2 0.6 0.5 0.6 0.5 0.6 0.5 0.5 0.5 0.6 0.1 0.1 0.1 0.1 0.2 0.1 0.1 0.2 0.1 0.1 Y24 0.2 0.2 0.2 0.2 0.2 0.1 0.2 0.2 0.1 0.2 0.2 0.2 0.1 0.1 0.1 0.1 0.2 0.1 0.1 0.2 0.6 0.6 0.6 0.5 0.6 0.6 0.6 0.5 0.6 0.1 0.1 0.1 0.1 0.1 0.1 0.1 0.2 0.1 0.1 Y25 0.1 0.2 0.1 0.2 0.1 0.1 0.1 0.1 0.1 0.2 0.1 0.2 0.2 0.1 0.1 0.1 0.2 0.1 0.1 0.2 0.7 0.7 0.5 0.5 0.5 0.7 0.6 0.6 0.7 0.1 0.1 0.1 0.1 0.1 0.1 0.1 0.1 0.1 0.1 Color legend Y26 0.2 0.2 0.2 0.2 0.2 0.2 0.3 0.2 0.1 0.2 0.2 0.2 0.2 0.1 0.1 0.1 0.1 0.1 0.1 0.1 0.5 0.6 0.6 0.6 0.5 0.6 0.6 0.5 0.6 0.1 0.1 0.1 0.1 0.1 0.1 0.1 0.1 0.1 0.1 C3 Y27 0.1 0.1 0.1 0.2 0.1 0.2 0.2 0.1 0.1 0.2 0.1 0.2 0.1 0.1 0.1 0.1 0.1 0.1 0.1 0.1 0.6 0.6 0.5 0.6 0.7 0.6 0.6 0.5 0.6 0.2 0.1 0.1 0.1 0.2 0.1 0.1 0.1 0.1 0.1 Y28 0.2 0.2 0.1 0.2 0.2 0.2 0.2 0.2 0.1 0.2 0.2 0.1 0.1 0.2 0.1 0.2 0.1 0.2 0.2 0.1 0.5 0.6 0.5 0.6 0.6 0.6 0.6 0.5 0.6 0.1 0.0 0.1 0.1 0.1 0.1 0.1 0.1 0.1 0.1 Y29 0.2 0.2 0.1 0.2 0.1 0.1 0.1 0.2 0.2 0.2 0.1 0.1 0.1 0.1 0.1 0.1 0.1 0.1 0.1 0.1 0.6 0.6 0.5 0.5 0.6 0.5 0.5 0.5 0.6 0.2 0.1 0.2 0.2 0.1 0.1 0.2 0.1 0.2 0.1 0.0 0.1 0.2 0.3 0.4 0.5 0.6 0.7 0.8 0.9 1.0 Y30 0.1 0.1 0.1 0.1 0.1 0.1 0.2 0.1 0.1 0.1 0.1 0.2 0.1 0.1 0.1 0.1 0.1 0.1 0.1 0.1 0.7 0.7 0.6 0.6 0.7 0.6 0.6 0.6 0.6 0.1 0.1 0.1 0.1 0.1 0.1 0.1 0.1 0.1 0.1 Y31 0.2 0.2 0.2 0.1 0.2 0.2 0.2 0.2 0.1 0.1 0.1 0.1 0.1 0.1 0.2 0.1 0.1 0.1 0.1 0.2 0.1 0.2 0.1 0.1 0.1 0.1 0.2 0.1 0.2 0.1 0.7 0.7 0.7 0.7 0.7 0.7 0.6 0.7 0.6 Y32 0.2 0.2 0.2 0.2 0.2 0.3 0.2 0.2 0.2 0.2 0.1 0.1 0.1 0.1 0.2 0.1 0.1 0.1 0.1 0.2 0.1 0.1 0.1 0.1 0.1 0.1 0.1 0.0 0.1 0.1 0.7 0.7 0.7 0.7 0.7 0.7 0.6 0.7 0.6 Y33 0.2 0.2 0.2 0.2 0.2 0.2 0.2 0.2 0.2 0.2 0.1 0.1 0.1 0.1 0.2 0.1 0.1 0.1 0.1 0.1 0.1 0.1 0.1 0.1 0.1 0.1 0.1 0.1 0.2 0.1 0.7 0.7 0.7 0.8 0.7 0.7 0.6 0.7 0.6 Y34 0.2 0.2 0.2 0.2 0.2 0.2 0.2 0.2 0.2 0.2 0.1 0.2 0.1 0.1 0.2 0.1 0.1 0.1 0.1 0.1 0.1 0.1 0.1 0.1 0.1 0.1 0.1 0.1 0.2 0.1 0.7 0.7 0.7 0.7 0.7 0.6 0.7 0.7 0.6 Y35 0.2 0.2 0.2 0.2 0.2 0.3 0.2 0.2 0.2 0.2 0.1 0.1 0.1 0.1 0.1 0.1 0.1 0.1 0.1 0.1 0.1 0.1 0.2 0.1 0.1 0.1 0.2 0.1 0.1 0.1 0.7 0.7 0.8 0.7 0.7 0.7 0.7 0.7 0.7 Y36 0.2 0.2 0.2 0.2 0.2 0.3 0.2 0.2 0.2 0.2 0.1 0.1 0.1 0.1 0.2 0.1 0.1 0.1 0.1 0.1 0.1 0.1 0.1 0.1 0.1 0.1 0.1 0.1 0.1 0.1 0.7 0.7 0.7 0.7 0.7 0.7 0.6 0.7 0.7 C4 Y37 0.2 0.2 0.2 0.2 0.2 0.3 0.2 0.3 0.2 0.2 0.1 0.1 0.1 0.1 0.2 0.1 0.1 0.2 0.1 0.2 0.1 0.1 0.1 0.1 0.1 0.1 0.1 0.1 0.2 0.1 0.7 0.7 0.7 0.6 0.7 0.7 0.6 0.7 0.6 Y38 0.2 0.2 0.2 0.2 0.2 0.2 0.2 0.2 0.2 0.2 0.1 0.2 0.1 0.1 0.3 0.2 0.1 0.1 0.1 0.1 0.1 0.1 0.2 0.2 0.1 0.1 0.1 0.1 0.1 0.1 0.6 0.6 0.6 0.7 0.7 0.6 0.6 0.7 0.6 Y39 0.2 0.2 0.2 0.2 0.2 0.2 0.2 0.2 0.2 0.1 0.1 0.1 0.1 0.1 0.2 0.1 0.1 0.1 0.1 0.1 0.1 0.1 0.1 0.1 0.1 0.1 0.1 0.1 0.2 0.1 0.7 0.7 0.7 0.7 0.7 0.7 0.7 0.7 0.7 Y40 0.3 0.2 0.3 0.2 0.2 0.2 0.3 0.2 0.3 0.2 0.1 0.2 0.1 0.1 0.2 0.2 0.1 0.1 0.1 0.2 0.1 0.1 0.1 0.1 0.1 0.1 0.1 0.1 0.1 0.1 0.6 0.6 0.6 0.6 0.7 0.7 0.6 0.6 0.7
C1 C2 C3 C4
C D
Co-occurrence Probability Matrix ‘CREB’ K=5
0.6 0.2 0.1 0.1 0.2 C1 0.2 0.8 0.1 0.0 0.0
0.1 0.1 0.7 0.1 0.0
C2 0.1 0.0 0.1 0.6 0.2
0.2 0.0 0.0 0.2 0.7
C3
Color0.0 legend0.1 0.2 0.3 0.4 0.5 0.6 0.7 0.8 0.9 1.0
C4 0.0 0.1 0.2 0.3 0.4 0.5 0.6 0.7 0.8 0.9 1.0
C5
C1 C2 C3 C4 C5
Supplementary Figure S1: The co-occurrence probability matrices are shown for the ‘‘Hypoxia’’ PFG (A-B) and the PFG ‘‘CREB’’ (C-D). Matrices show the measure of stability used in the Progeny Clustering. The Progeny Clustering first assigns cluster membership to the full data set, and then validates the clusters by constructing progenies out of existing ones by taking features independently. Each matrix represents the result for the optimal number of clusters and shows the average cluster results (iteration = 100, repeat = 10) of all mixed progenies that were generated (A, C). The matrix entry is 1 if two progenies are in the same cluster, and 0 if they are in a different cluster. For each cluster 10 progenies were generated, which are denoted as Y. If the cluster quality was higher the classification region is shown in darker red. False classification regions that contain progenies from different initial clusters are shown in blue. The simplified matrices (B, D) show the median probability scores. For the ‘‘Hypoxia’’ PFG (A, B) that had an optimal number of 4 clusters, clustering resulted in a median probability score of 0.7 for all progenies (range 0.6-0.7). For the PFG ‘‘CREB’’ (C, D) we found an optimal number of 5 clusters. The median of probability scores of all progenies was 0.7 (range 0.6-0.8), which shows that the stability of the clustering is quite robust.
Supplementary Fig. S2. Principal component analysis for the 95 pediatric acute myeloid leukemia samples stratified by source; peripheral blood (PB) samples or bone marrow samples (BM). From here we do not see clustering of samples based on their source type.
● ● PB ● BM 10
● ● ● ● ●
5 ● ● ● ● ●● ● ● ● ● ● ●● ● ● ● ● ●● ● ● ●● ● ● PC2 ● ● ●● ● ●● ●● ●● ● ● ●
0 ● ●● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ●● ● ●● ● ● ● ● ● ● ● ●●
− 5 ●● ● ●● ● ● ●
−5 0 5 10 15
PC1 A B
Cluster Cluster IGFBP2 YAP1 GAB2.pY452 6 C1 IGFBP2 JUNB YAP1 RICTOR.pT1135 GAB2.pY452 PIM2 JUNB SMAD5.pS463 RICTOR.pT1135 SMAD6 PIM2 SOCS2 C2 SMAD5.pS463 ERBB2.pY1248 SMAD6 INPP5D SOCS2 NF2.pS518 ERBB2.pY1248 6 RPTOR 4 INPP5D PRKCB.I NF2.pS518 SPP1 C3 RPTOR NRP1 PRKCB.I HIF1A SPP1 PIM1 NRP1 MCL1 HIF1A SFN PIM1 CCNB1 C4 MCL1 BIRC2 2 SFN 4 CCND1 CCNB1 ERBB2 BIRC2 YES1 CCND1 STAT6.pY641 ERBB2 TSC2.pT1462 C5 YES1 PIK3CA STAT6.pY641 NOTCH3 TSC2.pT1462 TAZ PIK3CA IRS1.pS1101 0 NOTCH3 XIAP TAZ 2 MET.pY1230_1234_1235 C6 IRS1.pS1101 EIF2AK2.pT451 XIAP HDAC3 MET.pY1230_1234_1235 TP53.pS15 EIF2AK2.pT451 CLPP HDAC3 DLX1 C7 TP53.pS15 FOXO3A CLPP CASP3.cl175 DLX1 PARP1.cl214 −2 FOXO3A CCND3 CASP3.cl175 0 LGALS3 PARP1.cl214 BCL2L11 C8 CCND3 CDKN1B LGALS3 YAP1p BCL2L11 AKT1_2_3.pT308 CDKN1B MDM2 YAP1p ODC1 AKT1_2_3.pT308 LCK −4 MDM2 SRC.pY416 ODC1 CASP9.cl330 LCK −2 SRC.pY416 BAK1 CASP9.cl330 MTOR.pS2448 BAK1 KDR MTOR.pS2448 CASP9 KDR FKHRL1 CASP9 CDKN2A FKHRL1 CASP7.cl198 CDKN2A CASP9.cl315 CASP7.cl198 DUSP6 CASP9.cl315 −4 PRKCA DUSP6 RPS6KB1.pT389 PRKCA PRKCD.pS645 RPS6KB1.pT389 BAX PRKCD.pS645 VASP BAX CBL VASP CDKN1B.pS10 CBL RPS6.pS235_236 CDKN1B.pS10 RPS6.pS240_244 RPS6.pS235_236 AKT1_2_3.pS473 RPS6.pS240_244 MAPK14.pT180Y182 AKT1_2_3.pS473 MAP2K1 MAPK14.pT180Y182 MAPK1 MAP2K1 INPPL1 MAPK1 PDK1.pS241 INPPL1 PDK1 PDK1.pS241 BECN1 PDK1 BID BECN1 MAPK9 BID PIK3R1_2 MAPK9 STAT3.pY705 PIK3R1_2 STAT3.pS727 STAT3.pY705 STAT3 STAT3.pS727 TSC2 STAT3 RELA TSC2 RICTOR RELA SIRT1 RICTOR STAT5A_B.pY694 SIRT1 SPI1 STAT5A_B.pY694 MAPK14 SPI1 PTEN MAPK14 ITGAL PTEN STAT1 ITGAL TAF4 STAT1 KIT TAF4 NR4A1 KIT PRKCA.pS657 NR4A1 TGM2 PRKCA.pS657 FN1 TGM2 GATA1 FN1 LEF1 GATA1 HIST3H3 LEF1 HIST3H3 CCNE2 CCNE2 H3K4Me2 H3K4Me2 GATA3 GATA3 H3K27Me3 H3K27Me3 BCL2L1 BCL2L1 STK11 STK11 NF2 NF2 TRIM24 TRIM24 BRCA2 BRCA2 HDAC2 HDAC2 YWHAZ YWHAZ XPO1 XPO1 PARK7 PARK7 CASP8 CASP8 BRAF BRAF RPS6 RPS6 MTOR MTOR HNRNPK HNRNPK NCL NCL TNK1 TNK1 FLI1 FLI1 CREB1 CREB1 DDX17 DDX17 LYN LYN SMAD3 SMAD3 EIF2AK2.pS51 EIF2AK2.pS51 TP53 TP53 CCNE1 CCNE1 RB1 RB1 MYC MYC STAT5A_B STAT5A_B RPS6KB1 RPS6KB1 SMAD5 SMAD5 BAD BAD MDM4 MDM4 SMAD4 SMAD4 TAZ.pS89 TAZ.pS89 DIABLO DIABLO ELK1.pS383 ELK1.pS383 KDM1A KDM1A WTAP WTAP NPM1.3542 NPM1.3542 EIF2AK2 EIF2AK2 SRC SRC GAB2 GAB2 CDKN1A CDKN1A HDAC6 HDAC6 EIF2S1 EIF2S1 EIF4E EIF4E PTPN11 PTPN11 AKT1 AKT1 SMAD2 SMAD2 CREB1.pS133 CREB1.pS133 SMAD2.pS245 SMAD2.pS245 CASP3 CASP3 STMN1 STMN1 BCL2 BCL2 PARP1 PARP1 SMAD2.pS465 SMAD2.pS465 GRP78 GRP78 CD74 CD74 CDK2 CDK2 MSI2 MSI2 SQSTM1 SQSTM1 CTNNA1 CTNNA1 ITGA2 ITGA2 CDK1 CDK1 PPARG PPARG CAV1 CAV1 BMI1 BMI1 PTK2 PTK2 NOTCH1.cl1744 NOTCH1.cl1744 ASNS ASNS VHL VHL HDAC1 HDAC1 ATF3 ATF3 EGFR EGFR IGF1R IGF1R ERN1 ERN1 SMAD1 SMAD1 SSBP2 SSBP2 RB1.pS807_811 RB1.pS807_811 CDK4 CDK4 HSPB1 HSPB1 BIRC5 BIRC5 H3K4Me3 H3K4Me3 WEE1 WEE1 JUN.pS73 JUN.pS73 STAT1.pY701 STAT1.pY701 CTNNB1 CTNNB1 ITGB3 ITGB3
Supplementary Figure S3: Unsupervised hierarchical clustering for all 95 AML patient samples. Unsupervised hierarchical clustering using the Ward linkage method (A) and the Progeny Clustering algorithm (coupled with k-means) (B) were applied to the full data set of proteins.
Signature
S1 S2 S3 S4 S5 S6 S7 S8
BIRC5 CAV1 CBLCAV1 CBLDDX17 FN1 DDX17 FOXO3A FN1HIF1A FOXO3AIGFBP2 INPP5D KDM1AHIF1A IGFBP2LGALS3 MAP2K1 INPP5D MAPK14 KDM1AMSI2 LGALS3MYC NOTCH3 NPM1.3542MAP2K1 MAPK14PARP1 PIM2 MSI2 PTEN SMAD2MYC NOTCH3SMAD2.pS465 SMAD5.pS463 SMAD6NPM1.3542 PARP1SOCS2 SRC.pY416 PIM2 SSBP2 TAF4PTEN SMAD2YAP1 YES1 S1 S2 S3 S4 S5 S6 S7 S8 SMAD2.pS465 SMAD5.pS463 SMAD6 Supplementary Figure S4. The minimal set of 30 antibodies that enable SOCS2 classification into the defined protein expression signatures. The 30 most discriminative proteins outSRC.pY416 of the 194 proteins were selected using Random Forest. Colors reflect median expressionSSBP2 levels for each signature relative to the normal CD34+ samples, ranged TAF4from the lowest (dark blue) to the highest (maroon). Proteins are listed alphabetically. YAP1
YES1 S1 S2 S3 S4 S5 S6 S7 S8 A B
Sample ● Sample Sample 25 ● CCNB1 RPS6 ● RICTOR ● ● ● AML patient TSC2 AML patient BRAF ●● RELA ●● EIF2S1 ● ● Cell line EIF4E ●● ● PTPN11 ●●● BECN1 20 ●●●● AKT1 Cell line ● ● SMAD2 ●●● GAB2.pY452 ● ● 5 ● STAT5A_B.pY694 ●●●●● STAT6.pY641 ● STAT3.pS727 ●●● STAT3.pY705 ● SIRT1 15 ● ● SMAD3 MTOR ●● ● ● CREB1 ● ● HNRNPK ●●●●● ● TNK1 ● ●●● BRCA2 ●●●● HDAC2 ●● ● TRIM24 ● ● DDX17 10 ● ●● ● KDM1A ● ● CCNE1 ●● FLI1 ● ● NCL ● ● ● MDM4 ● SMAD4 ● RPS6KB1 0 ● SMAD5 ● PARK7 5 ● NF2 STK11 BCL2L1 RB1 ● ●●● HIST3H3 ●● ● BAD ●● NOTCH1.cl1744 ●●●● ● SMAD2.pS465 ●●●●●● GAB2 0 ●● NPM1.3542 ●● ● ● ●● EIF2AK2 ●● ●●●●● ● STAT5A_B ● ● ● ● CREB1.pS133 PC2 ●●● ● ● HDAC6 ●●●●●● ● SMAD2.pS245 ●● ● CASP3 ● ● MAPK14 5 ●● ● ● CDKN1B −5 ● ● PDK1 ● ●● NF2.pS518 − ●●● ● SMAD6 ● ● NOTCH3 PIK3CA ● XIAP CCND1 ERBB2 ● BIRC2 −10 YES1 ● CLPP ● EIF2AK2.pT451 DLX1 HDAC3 RPTOR TAZ YAP1p SMAD5.pS463 PIM2 RICTOR.pT1135 PPARG 10 ● ITGA2 CDK2 MSI2 − CAV1 SFN ● MCL1 ● ● ● SPP1 HIF1A PIM1 GRP78 ● CD74 ● CDK1 SQSTM1 IGF1R BMI1 VHL ATF3 HDAC1 RPS6.pS240_244 ● CASP3.cl175 15 PARP1.cl214 RPS6.pS235_236
AKT1_2_3.pS473 − MAPK14.pT180Y182 STAT1 ITGAL LYN PTEN SPI1 CDKN1B.pS10 BAX PRKCD.pS645 −10 0 10 20 RPS6KB1.pT389 CASP9.cl330 BAK1 MTOR.pS2448 KDR STAT3 CASP9 FKHRL1 MDM2 ODC1 AKT1_2_3.pT308 CCND3 PC1 BID INPPL1 MAPK1 MAPK9 MAP2K1 PDK1.pS241 SRC.pY416 GATA3 LCK PRKCA CBL DUSP6 ASNS BCL2L11 CDKN2A PARP1 CASP7.cl198 CASP9.cl315 TGM2 SRC RB1.pS807_811 TP53 TP53.pS15 CDK4 CTNNB1 JUN.pS73 STAT1.pY701 SSBP2 PTK2 STMN1 WEE1 BCL2 HSPB1 LEF1 NR4A1 PRKCA.pS657 FN1 GATA1 KIT SMAD1 FOXO3A IGFBP2 H3K27Me3 SOCS2
Supplementary Figure S5. (A) Unsupervised hierarchical clustering (Ward linkage) for all mycoplasma negative cell lines samples (N=95) and the 95 acute myeloid leukemia patient samples showed a clear separation in overall proteomic patterns. Only one patient clusters within the cell lines. (B) Principal component analysis confirms a clear separation between patient samples and cell lines based on overall proteomic profiles.