Supplemental InformationSHP2 Is Required for BCR-ABL1-Induced Hematopoietic Neoplasia

Supplementary Figure S1. SHP2 is required for BCR-ABL1-evoked initiation of CML-like MPN.(a) Scheme of experiment to assess the requirement for SHP2 in initiation of CML-like MPN. (b-d) Engraftment in recipients of WT or Ptpn11fl/fl donor cells 12 days post-transplantation in (b) peripheral blood (P < 0.05), (c) spleen (P < 0.01), and (d) bone marrow (not significant) (n = 4). (e) Engraftment in recipients of WT (n = 11) or Ptpn11fl/fl (n = 13) donor cells 46 days post-

transplantation in peripheral blood (P < 0.05). (f) Spleen weight of recipients of WT (n = 11) or Ptpn11fl/fl (n = 13) donor cells (P < 0.01). (g) Histology of peripheral blood, bone marrow, spleen, and liver in typical WT mouse or recipients of WT or Ptpn11fl/fl cells infected with p210MIGFPCre virus (400x amplification).

Supplementary Figure S2. SHP2 is required for CML maintenance.(a) Scheme of experiment to assess the requirement for SHP2 in maintenance of CML-like MPN. (b-c) Post-transplant peripheral blood leukemic cell engraftment (b) and total white blood cell count (c) was monitored for each recipient. Arrows indicate time of injections with poly I:C. (d-e) Box-plot summary of peripheral blood leukemic engraftment level (d) and white blood cell count (e) in each group on Day 9 (before poly I:C induction), Day 17 (early post-induction), or Day 22-25 (later post-induction) post-transplantation. (*P < 0.05, n.s. not significant; ANOVA with Bonferroni post-test). Note that the Mx+pI:C and Mx-fl/fl+pI:C groups had comparable peripheral blood leukemic engraftment before or early after poly I:C induction, but leukemic engraftment was significantly impaired after prolonged SHP2 depletion. WBC counts were not significantly different between Mx+pI:C and Mx-fl/fl+pI:C mice even on Day 22-25 post-transplantation, most likely because only a few mice are left in the control group at this time, which blunts the sensitivity of the assay. (f) Statistical analysis of ratio of phosphorylated to total signaling protein levels from ≥5 biological replicates of the experiment shown in Figure 2c (*P < 0.05, n.s., not significant; 2-sided t tests with Benjamini-Hochberg adjustment for multiple comparisons).

Supplementary Figure S3. Progression of CML in recipients of MxCre;Ptpn11fl/fl donor cells is associated with imcomplete deletion of Ptpn11.Three recipients from the Mx-fl/fl + pI:C group were assessed for peripheral blood count and floxed Ptpn11 deletion from days 9 to day 37 post-transplantation. White blood cell count (x103/l) is shown in the upper table. Ptpn11 deletion was assessed by PCR; undeleted (“flox”) and deleted alleles are indicated. Notably, #28 and #30 succumbed to CML-like MPN, while #29, with efficient deletion of Ptpn11, remained alive and apparently normal.

Supplementary Figure S4. Assessment of SHP2 depletion on leukemic burden.(a) Statistical analysis of leukemic engraftment in Figure 3a. Engraftment is significantly lower in B/A-GFPCre -> Ptpn11fl/fl than in the other two groups (n = 5; mean ± s.e.m.; **P < 0.01, ***P < 0.001; N = 5 each; one-way ANOVA with Bonferroni post-test). (b) Peripheral blood leukemic engraftment on day 10 and day 21 post-transplantation in Mx and Mx-fl/fl groups (n = 5 for vehicle control groups and n = 10 for poly I:C groups; mean ± s.e.m.). Note that engraftment was comparable before, but significantly lower after poly I:C treatment (*P < 0.05, ***P < 0.001; one-way ANOVA with Bonferroni post-test), indicating the effect of poly I:C treatment itself and complicating the interpretation of the essentiality of SHP2 in disease maintenance.

Supplementary Figure S5. SHP2 is required for the proliferation of BCR/ABL1+ pre-B cells.(a) Scheme of experiments to assess the requirement for SHP2 in B cell proliferation. (b) 4-OH treatment does not affect proliferation of BCR-ABL1+ pre-B cells. A typical result from 4 separate experiments is shown; n.s. = no significant difference in slopes. (c) WT or BCR-ABL1+ Rosa26-CreER;Ptpn11fl/fl pre-B cells with intact (+/+) or deleted (/) Ptpn11 were cultured and SHP2 expression was monitored. Efficiency of Ptpn11 deletion was similar between WT and BCR-ABL1+ cells. (d) Statistical analysis of apoptosis levels shown in Figure 4b. SHP2 depletion did not influence apoptosis (n = 4; mean ± s.d.; n.s. = not significant; two-sided t test). (e) Statistical analysis of cell cycle stages shown in Figure 4c. SHP2 depletion significantly

increased the proportion of cells in G0, and decreased the proportion of cells in G1 or S-G2-M (n = 4; mean ± s.d.; **P < 0.01,***P < 0.001; two-sided t test with Benjamini-Hochberg adjustment for multiple comparisons).

Supplementary Figure S6. SHP2 is dispensable for B cell development and function.(a) SHP2 levels in splenocytes from Ptpn11fl/fl or Cd19tm1(cre)Cgn;Ptpn11fl/fl mice. (b) Representative flow cytometric analyses reveal that B cell development is not grossly affected by SHP2

deficiency. (c) SHP2 deficiency does not affect B cell proliferation (as assessed by thymidine incorporation) induced by various agonists. (d-e) Serum concentrations of IgM (d) and IgG3 (e) after NP-Ficoll immunization in Ptpn11fl/fl (Ctrl) or Cd19tm1(cre)Cgn;Ptpn11fl/fl (KO) mice.

Supplementary Figure S7. SHP2 inhibitor suppresses proliferation of BCR-ABL1+ pre-B cells.SHP2-replete (+/+) or -deficient (/) BCR-ABL1+ pre-B cells were treated with the allosteric SHP2 inhibitor SHP099 at the indicated concentrations for 2 days. (a) Relative viable cell numbers after 3-day cultures, pooled from 3 biological replicates. Viable cell numbers post-drug treatment were compared with the SHP2-replete 0M control (denoted by “*”) or the SHP2-deficient 0M control (denoted by “#”). ***P < 0.001, ###P < 0.001, n.s. not significant; ANOVA with Bonferroni post-test. (b) Representative immunoblot of SHP2-replete or SHP2-deficient cells in response to drug treatment.

Supplementary Figure S8. SFKs and ERK mediate the SHP2 requirement in BCR-ABL1+ pre-B cells.(a) Statistical analysis of ratio of phosphorylated to total signaling protein levels from 4 biological replicates of the experiment shown in Figure 5a (mean ± s.e.m.; *P < 0.05; 2-sided t test with Benjamini-Hochberg adjustment for multiple comparisons). (b) SHP2-replete BCR-ABL1+ pre-B cells were treated with the MEK/ERK inhibitor U0126 and/or the SFK inhibitor SU6656 at different concentrations, and compared with SHP2-deficient BCR-ABL1+ pre-B cells

by immunoblotting for the indicated proteins or phospho-epitopes (1-hour drug treatment, n = 3). U0126 specifically affects phospho-ERK, and SU6656 specifically affects phospho-SFK. (c) SHP2-deficient WT pre-B cells were treated with SU6656 (0, 1, 2M), and compared to SHP2-replete WT pre-B cells or SHP2-deficient BCR-ABL1+ pre-B cells by immunoblotting (1-hour treatment, n = 4). Total ERK2 serves as a loading control.

Supplementary Figure S9. SHP2 domains required for SFK and ERK activation.Statistical analysis of phospho-SFK(Y416) and phospho-ERK levels in Rosa26-CreER;Ptpn11fl/fl

BCR-ABL1+ cells from experiments in Figure 6b. Note that reconstitution with WT SHP2, but not the C459E or Y542F/Y580F mutant, restores ERK and SFK activity. (n = 3; mean ± s.e.m.; *P < 0.05, **P < 0.01, ***P < 0.001; ANOVA with Bonferroni post-test)

Supplementary Figure S10. SHP2 affects distinct transcriptional programs in WT and BCR-ABL1+ pre-B cells.(a) Unsupervised hierarchical clustering of RNA-seq data from: WT SHP2+/+ (WT_+/+), WT SHP2-/- (WT_-/-), BCR-ABL SHP2+/+ (BA_+/+), and BCR-ABL SHP2-/- (BA_-/-). (b) PCA of RNA-seq data from the four groups in panel (A). PC1 and PC2 separate the samples based on expression status of BCR-ABL1 and SHP2, respectively. (c) Hierarchical clustering of RNA-seq data from: WT SHP2+/+ (WT_+/+), WT SHP2-/- (WT_-/-), BCR-ABL SHP2+/+ (BA_+/+), and BCR-ABL SHP2-/- (BA_-/-), based on genes significantly regulated by SHP2 in either WT or BCR-ABL1+ cells (4 samples per group). (d) SHP2-regulated genes in WT or BCR-ABL1+ cells enrich for different GO terms. Bar graph (left) denotes significance of enrichment for each GO term in the SHP2-regulated gene sets. Bar graph on the right denotes the percentage of SHP2-regulated genes in each GO category in WT or BCR-ABL1+ cells.

Supplementary Figure S11. GSEA for signaling pathways regulating transcription in BCR-ABL1 in pre-B cells.(a) ERK MAPK targets are up-regulated, whereas (b) type I interferon response genes are down-regulated, in BCR-ABL1+, compared with WT, pre-B cells.

Supplementary Figure S12. Comparison of down-regulated gene sets by SHP2- or GAB2-depletion in BCR-ABL1+ pre-B cells.(a) Venn diagram illustrating genes regulated by SHP2 and/or GAB2 in BCR-ABL1+ pre-B cells. (b) The majority of gene sets (bold) down-regulated in SHP2-depleted BCR-ABL1+ pre-B cells are also down-regulated in GAB2-deficient cells, with comparable FDR q-values.

Supplementary Figure S13. MYC targets are regulated differentially by SHP2 in WT and BCR-ABL1+ pre-B cells.(a) GSEA plots of MYC-induced signatures from WT_-/- versus WT_+/+ or BA_-/- versus BA_+/+ cells. (b) Binding sites for MYC and its interactors are enriched differentially in genes down-regulated by SHP2 deficiency in WT or BCR-ABL1+ pre-B cells. (c) Glycolytic genes are up-regulated in response to SHP2 deficiency in WT cells, but down-regulated in SHP2-deficient BCR-ABL1+ (BA) cells. (d) Typical GSEA plots for glycolytic genes, comparing WT_-/- versus WT_+/+ (upper), or BA_-/- versus BA_+/+ (lower) cells.

Supplementary Figure S14. Interferon-alpha response genes are up-regulated by SHP2-deficiency only in BCR-ABL1+ pre-B cells.(a) Typical GSEA plot for IFN--induced genes, comparing BCR-ABL1+ SHP2-deficient (BA -/-) versus BCR-ABL1+ SHP2-replete (BA +/+) cells. (b) Several IFN- target genes are up-regulated in response to SHP2 depletion only in BCR-ABL1+ cells.

Supplementary Figure S15. Differential regulation of MYC is likely mediated by MXD3 and MXD4.(a) RNA-seq reveals that Myc mRNA is not affected by SHP2 deficiency in WT or BCR-ABL1+ pre-B cells (n = 4). (b) Representative immunoblots of WT or BCR-ABL1+, Rosa26-CreER or Rosa26-CreER; Ptpn11fl/fl pre-B cells, treated with 4-OH. Quantification of MYC levels reveals comparable regulation in WT and BCR-ABL1+ cells (2 biological replicates). (c) RNAseq reveals that Mxd3 and Mxd4 are up-regulated in response to SHP2 deficiency in BCR-ABL1+ (BA) cells, but not regulated by SHP2 in WT cells. (d) BCR-ABL1+ SHP2-deficient (-/-) or replete (+/+) pre-B cells were treated with U0126 and/or SU6656 at indicated concentrations for 2 days. Relative mRNA levels for Mxd4 were quantified (n = 4). Transcription levels were compared with SHP2-replete BCR-ABL1+ vehicle control (denoted by “*”) or SHP2-deficient control (denoted by “#”) groups. (*P < 0.05, **P < 0.01, ***P < 0.001, ##P < 0.01, ###P < 0.001; ANOVA with Bonferroni post-test).

Supplementary Table S1. Gene sets up-regulated in BCR-ABL1+ compared to WT pre-B cells.

NAME FDR q-val

SMID_BREAST_CANCER_RELAPSE_IN_LUNG_DN 0.00413043

PEDERSEN_METASTASIS_BY_ERBB2_ISOFORM_1 0.00509843

REACTOME_ERK_MAPK_TARGETS 0.022087663

WANG_ADIPOGENIC_GENES_REPRESSED_BY_SIRT1 0.039266393

HUNSBERGER_EXERCISE_REGULATED_GENES 0.035925426

SERVITJA_ISLET_HNF1A_TARGETS_DN 0.032819726

LI_PROSTATE_CANCER_EPIGENETIC 0.04460765

FUKUSHIMA_TNFSF11_TARGETS 0.04924761

GAUSSMANN_MLL_AF4_FUSION_TARGETS_D_UP 0.055580188

ACEVEDO_LIVER_CANCER_WITH_H3K27ME3_DN 0.07718506

Supplementary Table S2. Gene sets down-regulated in BCR-ABL1+ compared to WT pre-B cells.

NAME FDR q-val

ZHENG_GLIOBLASTOMA_PLASTICITY_DN 0.002913152

BENNETT_SYSTEMIC_LUPUS_ERYTHEMATOSUS 0.003397361

DIAZ_CHRONIC_MEYLOGENOUS_LEUKEMIA_DN 0.002587244

RADAEVA_RESPONSE_TO_IFNA1_UP 0.001940433

NABA_PROTEOGLYCANS 0.003866493

KRASNOSELSKAYA_ILF3_TARGETS_UP 0.00338372

LINDSTEDT_DENDRITIC_CELL_MATURATION_B 0.003302206

RODRIGUES_DCC_TARGETS_DN 0.007940454

REACTOME_INTERFERON_ALPHA_BETA_SIGNALING 0.009961274

MORI_PRE_BI_LYMPHOCYTE_DN 0.010421938

TSAI_RESPONSE_TO_RADIATION_THERAPY 0.015198747

DER_IFN_GAMMA_RESPONSE_UP 0.017651487

DER_IFN_ALPHA_RESPONSE_UP 0.035211198

ZHANG_INTERFERON_RESPONSE 0.040390052

WUNDER_INFLAMMATORY_RESPONSE_AND_CHOLESTEROL_UP 0.03834172

MORI_SMALL_PRE_BII_LYMPHOCYTE_UP 0.03594536

BROWNE_INTERFERON_RESPONSIVE_GENES 0.034628686

KAMIKUBO_MYELOID_CEBPA_NETWORK 0.034795098

UROSEVIC_RESPONSE_TO_IMIQUIMOD 0.070058644

MURATA_VIRULENCE_OF_H_PILORI 0.0686552

HOFFMANN_PRE_BI_TO_LARGE_PRE_BII_LYMPHOCYTE_UP 0.07352034

BROWNE_HCMV_INFECTION_30MIN_UP 0.08121635

MOSERLE_IFNA_RESPONSE 0.07857356

AZARE_NEOPLASTIC_TRANSFORMATION_BY_STAT3_UP 0.09142074

Supplementary Table S3. Top Reactome pathways for shared down-regulated genes in WT and BCR-ABL1+ pre-B cells.

Term Overlap P-value Adjusted P-value

MAPK targets/ Nuclear events mediated by MAP kinases_Homo sapiens_R-HSA-450282

3/30 0.0006 0.027

Negative regulation of MAPK pathway_Homo sapiens_R-HSA-5675221 3/40 0.0014 0.027

TRAF6 Mediated Induction of proinflammatory cytokines_Homo sapiens_R-HSA-168180

4/72 0.0006 0.027

MAP kinase activation in TLR cascade_Homo sapiens_R-HSA-450294 4/60 0.0003 0.027

Toll Like Receptor 9 (TLR9) Cascade_Homo sapiens_R-HSA-168138 4/88 0.0013 0.027

MyD88 dependent cascade initiated on endosome_Homo sapiens_R-HSA-975155

4/85 0.0011 0.027

Toll Like Receptor 3 (TLR3) Cascade_Homo sapiens_R-HSA-168164 4/97 0.0018 0.027

MyD88 cascade initiated on plasma membrane_Homo sapiens_R-HSA-975871

4/82 0.0010 0.027

Toll Like Receptor 7/8 (TLR7/8) Cascade_Homo sapiens_R-HSA-168181 4/85 0.0011 0.027

TRAF6 mediated induction of NFkB and MAP kinases upon TLR7/8 or 9 activation_Homo sapiens_R-HSA-975138

4/83 0.0010 0.027

TRIF-mediated TLR3/TLR4 signaling_Homo sapiens_R-HSA-937061 4/97 0.0018 0.027

Toll Like Receptor 10 (TLR10) Cascade_Homo sapiens_R-HSA-168142 4/82 0.0010 0.027

MyD88-independent TLR3/TLR4 cascade_Homo sapiens_R-HSA-166166 4/97 0.0018 0.027

Toll Like Receptor 5 (TLR5) Cascade_Homo sapiens_R-HSA-168176 4/82 0.0010 0.027

Toll Like Receptor 2 (TLR2) Cascade_Homo sapiens_R-HSA-181438 4/92 0.0015 0.027

Toll Like Receptor TLR1:TLR2 Cascade_Homo sapiens_R-HSA-168179 4/92 0.0015 0.027

Toll Like Receptor TLR6:TLR2 Cascade_Homo sapiens_R-HSA-168188 4/92 0.0015 0.027

MyD88:Mal cascade initiated on plasma membrane_Homo sapiens_R-HSA-166058

4/92 0.0015 0.027

Activated TLR4 signalling_Homo sapiens_R-HSA-166054 4/112 0.0030 0.041

Toll Like Receptor 4 (TLR4) Cascade_Homo sapiens_R-HSA-166016 4/122 0.0041 0.046

ERKs are inactivated_Homo sapiens_R-HSA-202670 2/12 0.0023 0.033

Heparan sulfate/heparin (HS-GAG) metabolism_Homo sapiens_R-HSA-1638091

3/54 0.0032 0.041

Glycosaminoglycan metabolism_Homo sapiens_R-HSA-1630316 4/121 0.0040 0.046

tRNA processing in the nucleus_Homo sapiens_R-HSA-6784531 3/57 0.0037 0.046

Metabolism of amino acids and derivatives_Homo sapiens_R-HSA-71291 6/335 0.0081 0.075

Toll-Like Receptors Cascades_Homo sapiens_R-HSA-168898 4/140 0.0065 0.066

Methionine salvage pathway_Homo sapiens_R-HSA-1237112 2/6 0.0007 0.027

ERK/MAPK targets_Homo sapiens_R-HSA-198753 2/21 0.0063 0.066

Major pathway of rRNA processing in the nucleolus_Homo sapiens_R-HSA-6791226

4/166 0.0116 0.100

HS-GAG degradation_Homo sapiens_R-HSA-2024096 2/21 0.0063 0.066

Nuclear Events (kinase and transcription factor activation)_Homo sapiens_R-HSA-198725

2/24 0.0080 0.075

RAF-independent MAPK1/3 activation_Homo sapiens_R-HSA-112409 2/23 0.0074 0.073

Supplementary Table S4. Top Reactome pathways for shared up-regulated genes in WT and BCR-ABL1+ pre-B cells.

Term Overlap P-value Adjusted P-value

Mitochondrial Fatty Acid Beta-Oxidation_Homo sapiens_R-HSA-77289 2/17 0.006 0.29

Chemokine receptors bind chemokines_Homo sapiens_R-HSA-380108 3/56 0.005 0.29

Platelet degranulation_Homo sapiens_R-HSA-114608 4/105 0.004 0.29

Response to elevated platelet cytosolic Ca2+_Homo sapiens_R-HSA-76005 4/110 0.005 0.29

VEGF binds to VEGFR leading to receptor dimerization_Homo sapiens_R-HSA-195399

2/8 0.002 0.24

VEGF ligand-receptor interactions_Homo sapiens_R-HSA-194313 2/8 0.002 0.24

Signaling by VEGF_Homo sapiens_R-HSA-194138 6/328 0.015 0.52

VEGFA-VEGFR2 Pathway_Homo sapiens_R-HSA-4420097 5/320 0.047 0.52

VEGFR2 mediated cell proliferation_Homo sapiens_R-HSA-5218921 4/248 0.067 0.52

Fatty acid, triacylglycerol, and ketone body metabolism_Homo sapiens_R-HSA-535734

4/217 0.045 0.52

Supplementary Table S5. Top enriched GO Biological Process terms for genes regulated by SHP2 in WT pre-B cells.

Term PValue FDR

GO:0002376~immune system process 1.01E-05 0.024

GO:0005975~carbohydrate metabolic process 4.13E-05 0.048

GO:0008152~metabolic process 4.27E-05 0.033

GO:0006955~immune response 8.47E-05 0.049

GO:0006006~glucose metabolic process 9.27E-05 0.043

GO:0009987~cellular process 9.35E-05 0.036

GO:0005996~monosaccharide metabolic process 1.04E-04 0.035

GO:0006096~glycolysis 1.08E-04 0.032

GO:0044262~cellular carbohydrate metabolic process 1.62E-04 0.042

GO:0019318~hexose metabolic process 2.35E-04 0.054

GO:0019320~hexose catabolic process 3.62E-04 0.075

GO:0006007~glucose catabolic process 3.62E-04 0.075

GO:0046365~monosaccharide catabolic process 4.71E-04 0.089

GO:0055114~oxidation reduction 5.00E-04 0.087

Supplementary Table S6. Top enriched GO Biological Process terms for genes regulated by SHP2 in BCR-ABL1+ pre-B cells.

Term PValue FDR

GO:0009987~cellular process 3.27E-23 1.06E-19

GO:0044237~cellular metabolic process 1.56E-16 1.81E-13

GO:0008152~metabolic process 7.14E-14 7.74E-11

GO:0044238~primary metabolic process 8.94E-14 7.27E-11

GO:0044267~cellular protein metabolic process 5.55E-12 3.61E-09

GO:0044260~cellular macromolecule metabolic process 4.64E-11 2.51E-08

GO:0043170~macromolecule metabolic process 3.80E-09 1.77E-06

GO:0019538~protein metabolic process 2.14E-08 8.70E-06

GO:0044085~cellular component biogenesis 8.86E-08 3.20E-05

GO:0044249~cellular biosynthetic process 4.22E-07 1.37E-04

GO:0009058~biosynthetic process 1.81E-06 5.35E-04

GO:0006412~translation 3.33E-06 9.02E-04

GO:0043412~biopolymer modification 3.55E-06 8.88E-04

GO:0034622~cellular macromolecular complex assembly 7.86E-06 1.82E-03

GO:0065003~macromolecular complex assembly 9.13E-06 1.98E-03

GO:0006464~protein modification process 1.18E-05 2.39E-03

GO:0022607~cellular component assembly 1.86E-05 3.56E-03

GO:0043933~macromolecular complex subunit organization 2.56E-05 4.61E-03

GO:0034621~cellular macromolecular complex subunit organization 2.94E-05 5.02E-03

GO:0006334~nucleosome assembly 5.60E-05 9.07E-03

GO:0010467~gene expression 5.83E-05 8.98E-03

GO:0044262~cellular carbohydrate metabolic process 6.02E-05 8.85E-03

GO:0031497~chromatin assembly 8.20E-05 1.15E-02

GO:0034728~nucleosome organization 9.86E-05 1.33E-02

GO:0065004~protein-DNA complex assembly 9.86E-05 1.33E-02

GO:0034645~cellular macromolecule biosynthetic process 1.14E-04 1.48E-02

GO:0009059~macromolecule biosynthetic process 1.49E-04 1.85E-02

GO:0048002~antigen processing and presentation of peptide antigen 1.56E-04 1.86E-02

GO:0008283~cell proliferation 1.63E-04 1.87E-02

GO:0042127~regulation of cell proliferation 1.97E-04 2.19E-02

GO:0019320~hexose catabolic process 5.11E-04 5.39E-02

GO:0006007~glucose catabolic process 5.11E-04 5.39E-02

GO:0002376~immune system process 5.13E-04 5.24E-02

GO:0016265~death 5.21E-04 5.15E-02

GO:0006915~apoptosis 5.48E-04 5.25E-02

GO:0043687~post-translational protein modification 5.61E-04 5.23E-02

GO:0002478~antigen processing and presentation of exogenous peptide antigen

5.79E-04 5.23E-02

GO:0006950~response to stress 5.81E-04 5.12E-02

GO:0006333~chromatin assembly or disassembly 5.89E-04 5.05E-02

GO:0006996~organelle organization 6.33E-04 5.27E-02

GO:0008219~cell death 7.36E-04 5.95E-02

GO:0046365~monosaccharide catabolic process 7.53E-04 5.94E-02

GO:0005975~carbohydrate metabolic process 8.24E-04 6.33E-02

GO:0044255~cellular lipid metabolic process 8.41E-04 6.30E-02

GO:0042254~ribosome biogenesis 8.54E-04 6.25E-02

GO:0012501~programmed cell death 8.55E-04 6.12E-02

GO:0006066~alcohol metabolic process 1.14E-03 7.89E-02

GO:0006139~nucleobase, nucleoside, nucleotide and nucleic acid metabolic process

1.22E-03 8.29E-02

GO:0010627~regulation of protein kinase cascade 1.27E-03 8.44E-02

GO:0006807~nitrogen compound metabolic process 1.29E-03 8.37E-02

GO:0034641~cellular nitrogen compound metabolic process 1.33E-03 8.47E-02

GO:0006096~glycolysis 1.36E-03 8.44E-02

GO:0006006~glucose metabolic process 1.42E-03 8.64E-02

GO:0048514~blood vessel morphogenesis 1.49E-03 8.89E-02

GO:0048523~negative regulation of cellular process 1.50E-03 8.79E-02

GO:0001944~vasculature development 1.58E-03 9.07E-02

GO:0008610~lipid biosynthetic process 1.58E-03 8.95E-02

GO:0019882~antigen processing and presentation 1.61E-03 8.94E-02

GO:0001914~regulation of T cell mediated cytotoxicity 1.66E-03 9.03E-02

GO:0005996~monosaccharide metabolic process 1.67E-03 8.94E-02

GO:0034470~ncRNA processing 1.69E-03 8.90E-02

GO:0001568~blood vessel development 1.91E-03 9.85E-02

GO:0006457~protein folding 1.91E-03 9.70E-02

Supplementary Table S7. Gene sets down-regulated in SHP2-deficient, compared with SHP2-replete, BCR-ABL1+ pre-B cells.

NAME FDR q-val

SCHLOSSER_MYC_TARGETS_REPRESSED_BY_SERUM 8.24E-04

REACTOME_GLYCOLYSIS 4.12E-04

SERVITJA_ISLET_HNF1A_TARGETS_DN 5.48E-04

VANDESLUIS_COMMD1_TARGETS_GROUP_3_UP 6.13E-04

MOOTHA_GLUCONEOGENESIS 9.81E-04

FARDIN_HYPOXIA_11 0.001367925

SEMENZA_HIF1_TARGETS 0.001172507

WANG_ADIPOGENIC_GENES_REPRESSED_BY_SIRT1 0.002463047

TONKS_TARGETS_OF_RUNX1_RUNX1T1_FUSION_SUSTAINED_IN_MONOCYTE_UP 0.003291915

MILI_PSEUDOPODIA_HAPTOTAXIS_UP 0.004276552

MARTORIATI_MDM4_TARGETS_NEUROEPITHELIUM_UP 0.005760686

ZHANG_BREAST_CANCER_PROGENITORS_UP 0.006105966

REACTOME_GLUCONEOGENESIS 0.011090335

BOYAULT_LIVER_CANCER_SUBCLASS_G3_UP 0.019543504

REACTOME_METABOLISM_OF_NON_CODING_RNA 0.026045822

KIM_MYC_AMPLIFICATION_TARGETS_UP 0.024674453

MOOTHA_GLYCOLYSIS 0.023319084

PEDERSEN_METASTASIS_BY_ERBB2_ISOFORM_1 0.022068854

BOYLAN_MULTIPLE_MYELOMA_D_CLUSTER_UP 0.02286336

KARLSSON_TGFB1_TARGETS_UP 0.023126012

MARTORIATI_MDM4_TARGETS_FETAL_LIVER_UP 0.023474187

REACTOME_DEADENYLATION_DEPENDENT_MRNA_DECAY 0.024918603

KEGG_RNA_DEGRADATION 0.027094832

STEIN_ESRRA_TARGETS_RESPONSIVE_TO_ESTROGEN_UP 0.02699758

REACTOME_PYRUVATE_METABOLISM 0.029119607

SCHUHMACHER_MYC_TARGETS_UP 0.028315997

BROWN_MYELOID_CELL_DEVELOPMENT_DN 0.027480539

RAMALHO_STEMNESS_UP 0.028478226

IVANOVA_HEMATOPOIESIS_INTERMEDIATE_PROGENITOR 0.028035788

PID_MYC_ACTIV_PATHWAY 0.029987482

NIKOLSKY_BREAST_CANCER_8Q12_Q22_AMPLICON 0.031093385

GARGALOVIC_RESPONSE_TO_OXIDIZED_PHOSPHOLIPIDS_GREEN_UP 0.03068788

AMIT_EGF_RESPONSE_60_HELA 0.04123479

ELVIDGE_HIF1A_TARGETS_DN 0.04322127

PENG_GLUTAMINE_DEPRIVATION_DN 0.043138128

DANG_MYC_TARGETS_UP 0.04290445

KIM_HYPOXIA 0.04196767

LEONARD_HYPOXIA 0.043013588

Supplementary Table S8. Gene sets down-regulated in GAB2-deficient vs GAB2-replete BCR-ABL1+ pre-B cells.

NAME FDR q-val

WONG_EMBRYONIC_STEM_CELL_CORE 0

ZHANG_TLX_TARGETS_60HR_DN 0

MANALO_HYPOXIA_DN 0

ROSTY_CERVICAL_CANCER_PROLIFERATION_CLUSTER 0

KOBAYASHI_EGFR_SIGNALING_24HR_DN 0

SOTIRIOU_BREAST_CANCER_GRADE_1_VS_3_UP 0

DUTERTRE_ESTRADIOL_RESPONSE_24HR_UP 0

HOFFMANN_LARGE_TO_SMALL_PRE_BII_LYMPHOCYTE_UP 0

CROONQUIST_IL6_DEPRIVATION_DN 0

PENG_GLUTAMINE_DEPRIVATION_DN 0

ZHANG_TLX_TARGETS_DN 0

WINNEPENNINCKX_MELANOMA_METASTASIS_UP 0

BURTON_ADIPOGENESIS_3 0

GRAHAM_CML_DIVIDING_VS_NORMAL_QUIESCENT_UP 0

SHEDDEN_LUNG_CANCER_POOR_SURVIVAL_A6 0

MUELLER_PLURINET 0

REACTOME_MITOTIC_M_M_G1_PHASES 0

ZHOU_CELL_CYCLE_GENES_IN_IR_RESPONSE_24HR 0

SCHLOSSER_MYC_TARGETS_REPRESSED_BY_SERUM 0

REACTOME_DNA_REPLICATION 0

FOURNIER_ACINAR_DEVELOPMENT_LATE_2 0

GRAHAM_NORMAL_QUIESCENT_VS_NORMAL_DIVIDING_DN 0

ZHANG_TLX_TARGETS_36HR_DN 0

REACTOME_MRNA_PROCESSING 0

CROONQUIST_NRAS_SIGNALING_DN 0

BENPORATH_PROLIFERATION 0

REACTOME_PROCESSING_OF_CAPPED_INTRON_CONTAINING_PRE_MRNA 0

BLUM_RESPONSE_TO_SALIRASIB_DN 0

PENG_RAPAMYCIN_RESPONSE_DN 0

MISSIAGLIA_REGULATED_BY_METHYLATION_DN 0

WONG_MITOCHONDRIA_GENE_MODULE 0

REACTOME_M_G1_TRANSITION 0

RHODES_UNDIFFERENTIATED_CANCER 0

FUJII_YBX1_TARGETS_DN 0

YU_MYC_TARGETS_UP 0

ISHIDA_E2F_TARGETS 0

MOOTHA_HUMAN_MITODB_6_2002 0

PENG_LEUCINE_DEPRIVATION_DN 0

ZHOU_CELL_CYCLE_GENES_IN_IR_RESPONSE_6HR 0

WHITEFORD_PEDIATRIC_CANCER_MARKERS 0

KANG_DOXORUBICIN_RESISTANCE_UP 0

CHANG_CYCLING_GENES 0

LI_WILMS_TUMOR_VS_FETAL_KIDNEY_1_DN 0

PUJANA_XPRSS_INT_NETWORK 0

REACTOME_G1_S_TRANSITION 0

REACTOME_S_PHASE 0

YAO_TEMPORAL_RESPONSE_TO_PROGESTERONE_CLUSTER_17 0

REACTOME_CELL_CYCLE_MITOTIC 0

BASAKI_YBX1_TARGETS_UP 0

REACTOME_METABOLISM_OF_RNA 0

ZHAN_MULTIPLE_MYELOMA_PR_UP 0

RUIZ_TNC_TARGETS_DN 0

PUJANA_BRCA_CENTERED_NETWORK 0

SCHUHMACHER_MYC_TARGETS_UP 0

MOOTHA_MITOCHONDRIA 0

GARY_CD5_TARGETS_DN 0

KEGG_SPLICEOSOME 0

KAUFFMANN_MELANOMA_RELAPSE_UP 0

TARTE_PLASMA_CELL_VS_PLASMABLAST_DN 0

REACTOME_SYNTHESIS_OF_DNA 0

RHEIN_ALL_GLUCOCORTICOID_THERAPY_DN 0

DANG_MYC_TARGETS_UP 0

YAO_TEMPORAL_RESPONSE_TO_PROGESTERONE_CLUSTER_11 0

REN_BOUND_BY_E2F 0

MARKEY_RB1_ACUTE_LOF_UP 0

BIDUS_METASTASIS_UP 0

CHANG_CORE_SERUM_RESPONSE_UP 0

VECCHI_GASTRIC_CANCER_EARLY_UP 0

WANG_RESPONSE_TO_GSK3_INHIBITOR_SB216763_DN 0

KONG_E2F3_TARGETS 0

SCHLOSSER_MYC_TARGETS_AND_SERUM_RESPONSE_DN 0

REACTOME_MRNA_SPLICING 0

REACTOME_CELL_CYCLE_CHECKPOINTS 0

BENPORATH_ES_1 0

REACTOME_RESPIRATORY_ELECTRON_TRANSPORT_ATP_SYNTHESIS_BY_CHEMIOSMOTIC_COUPLING_AND_HEAT_PRODUCTION_BY_UNCOUPLING_PROTEINS_

0

BOYAULT_LIVER_CANCER_SUBCLASS_G3_UP 0

REACTOME_INFLUENZA_LIFE_CYCLE 0

YAO_TEMPORAL_RESPONSE_TO_PROGESTERONE_CLUSTER_14 0

TANG_SENESCENCE_TP53_TARGETS_DN 0

REACTOME_TCA_CYCLE_AND_RESPIRATORY_ELECTRON_TRANSPORT 0

REACTOME_MITOTIC_G1_G1_S_PHASES 0

REACTOME_LATE_PHASE_OF_HIV_LIFE_CYCLE 0

REACTOME_G2_M_CHECKPOINTS 0

SARRIO_EPITHELIAL_MESENCHYMAL_TRANSITION_UP 0

HORIUCHI_WTAP_TARGETS_DN 0

LY_AGING_OLD_DN 0

CHIANG_LIVER_CANCER_SUBCLASS_UNANNOTATED_DN 0

SONG_TARGETS_OF_IE86_CMV_PROTEIN 0

AFFAR_YY1_TARGETS_DN 0

LINDGREN_BLADDER_CANCER_CLUSTER_3_UP 1.10E-05

REACTOME_TRANSLATION 1.08E-05

BURTON_ADIPOGENESIS_PEAK_AT_24HR 1.07E-05

YAO_TEMPORAL_RESPONSE_TO_PROGESTERONE_CLUSTER_13 1.06E-05

PAL_PRMT5_TARGETS_UP 1.05E-05

REACTOME_ASSEMBLY_OF_THE_PRE_REPLICATIVE_COMPLEX 2.02E-05

GRADE_COLON_AND_RECTAL_CANCER_UP 2.00E-05

MOOTHA_VOXPHOS 1.98E-05

REACTOME_RESPIRATORY_ELECTRON_TRANSPORT 1.96E-05

REACTOME_REGULATION_OF_MITOTIC_CELL_CYCLE 1.94E-05

REACTOME_MITOTIC_PROMETAPHASE 1.92E-05

REACTOME_METABOLISM_OF_NON_CODING_RNA 1.90E-05

GROSS_HYPOXIA_VIA_HIF1A_UP 1.88E-05

GARCIA_TARGETS_OF_FLI1_AND_DAX1_DN 1.86E-05

REACTOME_METABOLISM_OF_MRNA 1.85E-05

REACTOME_CELL_CYCLE 1.83E-05

OXFORD_RALA_OR_RALB_TARGETS_UP 1.81E-05

MORI_LARGE_PRE_BII_LYMPHOCYTE_UP 2.69E-05

REACTOME_HOST_INTERACTIONS_OF_HIV_FACTORS 2.66E-05

REACTOME_ACTIVATION_OF_ATR_IN_RESPONSE_TO_REPLICATION_STRESS 2.64E-05

REACTOME_RNA_POL_II_TRANSCRIPTION 2.61E-05

ODONNELL_TFRC_TARGETS_DN 5.99E-05

KARLSSON_TGFB1_TARGETS_UP 5.94E-05

MOLENAAR_TARGETS_OF_CCND1_AND_CDK4_DN 5.89E-05

PUJANA_BREAST_CANCER_WITH_BRCA1_MUTATED_UP 5.84E-05

REACTOME_APC_C_CDH1_MEDIATED_DEGRADATION_OF_CDC20_AND_OTHER_APC_C_CDH1_TARGETED_PROTEINS_IN_LATE_MITOSIS_EARLY_G1

6.62E-05

VANTVEER_BREAST_CANCER_METASTASIS_DN 6.57E-05

NAKAMURA_CANCER_MICROENVIRONMENT_DN 6.51E-05

LEE_LIVER_CANCER_SURVIVAL_DN 6.45E-05

PUJANA_BRCA2_PCC_NETWORK 6.40E-05

FERREIRA_EWINGS_SARCOMA_UNSTABLE_VS_STABLE_UP 7.12E-05

KEGG_PARKINSONS_DISEASE 7.06E-05

KAMMINGA_EZH2_TARGETS 7.00E-05

REACTOME_ACTIVATION_OF_THE_PRE_REPLICATIVE_COMPLEX 6.95E-05

REACTOME_HIV_INFECTION 6.89E-05

REACTOME_TRANSPORT_OF_MATURE_TRANSCRIPT_TO_CYTOPLASM 6.84E-05

ZHANG_RESPONSE_TO_CANTHARIDIN_DN 6.78E-05

REACTOME_MITOCHONDRIAL_PROTEIN_IMPORT 8.19E-05

REACTOME_DNA_STRAND_ELONGATION 8.88E-05

WINTER_HYPOXIA_UP 8.81E-05

MITSIADES_RESPONSE_TO_APLIDIN_DN 9.46E-05

ZAMORA_NOS2_TARGETS_UP 1.08E-04

REACTOME_MRNA_SPLICING_MINOR_PATHWAY 1.22E-04

REACTOME_APC_C_CDC20_MEDIATED_DEGRADATION_OF_MITOTIC_PROTEINS 1.21E-04

MALONEY_RESPONSE_TO_17AAG_DN 1.41E-04

REACTOME_CDT1_ASSOCIATION_WITH_THE_CDC6_ORC_ORIGIN_COMPLEX 1.47E-04

PID_FANCONI_PATHWAY 1.60E-04

PID_MYC_ACTIV_PATHWAY 1.79E-04

ODONNELL_TARGETS_OF_MYC_AND_TFRC_DN 1.84E-04

REACTOME_AUTODEGRADATION_OF_CDH1_BY_CDH1_APC_C 1.83E-04

REACTOME_INFLUENZA_VIRAL_RNA_TRANSCRIPTION_AND_REPLICATION 2.15E-04

MORI_IMMATURE_B_LYMPHOCYTE_DN 2.40E-04

WANG_ADIPOGENIC_GENES_REPRESSED_BY_SIRT1 2.38E-04

REACTOME_3_UTR_MEDIATED_TRANSLATIONAL_REGULATION 2.90E-04

EGUCHI_CELL_CYCLE_RB1_TARGETS 3.07E-04

ZHANG_BREAST_CANCER_PROGENITORS_UP 3.24E-04

FRASOR_RESPONSE_TO_SERM_OR_FULVESTRANT_DN 3.68E-04

AMUNDSON_GAMMA_RADIATION_RESPONSE 4.04E-04

PID_AURORA_B_PATHWAY 4.08E-04

VERNELL_RETINOBLASTOMA_PATHWAY_UP 4.05E-04

BURTON_ADIPOGENESIS_PEAK_AT_16HR 4.15E-04

DANG_REGULATED_BY_MYC_UP 4.31E-04

REACTOME_ACTIVATION_OF_THE_MRNA_UPON_BINDING_OF_THE_CAP_BINDING_COMPLEX_AND_EIFS_AND_SUBSEQUENT_BINDING_TO_43S

4.59E-04

REACTOME_P53_INDEPENDENT_G1_S_DNA_DAMAGE_CHECKPOINT 4.81E-04

REACTOME_DESTABILIZATION_OF_MRNA_BY_AUF1_HNRNP_D0 4.78E-04

YAO_TEMPORAL_RESPONSE_TO_PROGESTERONE_CLUSTER_10 4.87E-04

GOLDRATH_ANTIGEN_RESPONSE 5.13E-04

REACTOME_HIV_LIFE_CYCLE 5.22E-04

RHODES_CANCER_META_SIGNATURE 5.55E-04

BORCZUK_MALIGNANT_MESOTHELIOMA_UP 5.93E-04

FARMER_BREAST_CANCER_CLUSTER_2 6.07E-04

REACTOME_REGULATION_OF_MRNA_STABILITY_BY_PROTEINS_THAT_BIND_AU_RICH_ELEMENTS

6.03E-04

MOREAUX_B_LYMPHOCYTE_MATURATION_BY_TACI_DN 5.99E-04

KEGG_PROTEASOME 5.96E-04

LE_EGR2_TARGETS_UP 5.92E-04

REACTOME_ORC1_REMOVAL_FROM_CHROMATIN 5.94E-04

KEGG_DNA_REPLICATION 5.90E-04

UDAYAKUMAR_MED1_TARGETS_UP 6.10E-04

JUBAN_TARGETS_OF_SPI1_AND_FLI1_DN 6.56E-04

KEGG_HUNTINGTONS_DISEASE 6.75E-04

REACTOME_CDK_MEDIATED_PHOSPHORYLATION_AND_REMOVAL_OF_CDC6 7.04E-04

REACTOME_TRNA_AMINOACYLATION 7.00E-04

WHITFIELD_CELL_CYCLE_LITERATURE 6.96E-04

REACTOME_VIF_MEDIATED_DEGRADATION_OF_APOBEC3G 7.20E-04

REICHERT_MITOSIS_LIN9_TARGETS 7.37E-04

STARK_PREFRONTAL_CORTEX_22Q11_DELETION_DN 7.49E-04

CHEMNITZ_RESPONSE_TO_PROSTAGLANDIN_E2_UP 7.61E-04

CHAUHAN_RESPONSE_TO_METHOXYESTRADIOL_UP 7.89E-04

REACTOME_METABOLISM_OF_PROTEINS 7.90E-04

GOLDRATH_HOMEOSTATIC_PROLIFERATION 7.91E-04

GREENBAUM_E2A_TARGETS_UP 7.86E-04

PID_PLK1_PATHWAY 8.13E-04

LEE_EARLY_T_LYMPHOCYTE_UP 8.40E-04

BURTON_ADIPOGENESIS_5 8.50E-04

IRITANI_MAD1_TARGETS_DN 8.51E-04

KEGG_OXIDATIVE_PHOSPHORYLATION 8.72E-04

REACTOME_E2F_MEDIATED_REGULATION_OF_DNA_REPLICATION 9.13E-04

MENSSEN_MYC_TARGETS 9.08E-04

REACTOME_SCF_BETA_TRCP_MEDIATED_DEGRADATION_OF_EMI1 0.001043388

REACTOME_NONSENSE_MEDIATED_DECAY_ENHANCED_BY_THE_EXON_JUNCTION_COMPLEX

0.001132647

PID_ATR_PATHWAY 0.001166339

ABRAMSON_INTERACT_WITH_AIRE 0.001209579

CHICAS_RB1_TARGETS_GROWING 0.001217927

REACTOME_SRP_DEPENDENT_COTRANSLATIONAL_PROTEIN_TARGETING_TO_MEMBRANE

0.001240648

REACTOME_CLEAVAGE_OF_GROWING_TRANSCRIPT_IN_THE_TERMINATION_REGION_ 0.001306934

BILANGES_RAPAMYCIN_SENSITIVE_VIA_TSC1_AND_TSC2 0.001329559

NADERI_BREAST_CANCER_PROGNOSIS_UP 0.001322776

REACTOME_INTERACTIONS_OF_VPR_WITH_HOST_CELLULAR_PROTEINS 0.001339796

KEGG_RIBOSOME 0.001385502

SHIPP_DLBCL_VS_FOLLICULAR_LYMPHOMA_UP 0.001440288

MOREAUX_MULTIPLE_MYELOMA_BY_TACI_DN 0.001451891

REACTOME_TRANSPORT_OF_RIBONUCLEOPROTEINS_INTO_THE_HOST_NUCLEUS 0.001449419

NAKAYAMA_SOFT_TISSUE_TUMORS_PCA2_UP 0.001451505

REACTOME_TRANSPORT_OF_MATURE_MRNA_DERIVED_FROM_AN_INTRONLESS_TRANSCRIPT

0.001476717

TOYOTA_TARGETS_OF_MIR34B_AND_MIR34C 0.001524796

FURUKAWA_DUSP6_TARGETS_PCI35_DN 0.001641386

KEGG_AMINOACYL_TRNA_BIOSYNTHESIS 0.00164258

REACTOME_CYCLIN_E_ASSOCIATED_EVENTS_DURING_G1_S_TRANSITION_ 0.001643775

REACTOME_EXTENSION_OF_TELOMERES 0.001739919

CHIANG_LIVER_CANCER_SUBCLASS_PROLIFERATION_UP 0.001803635

HESS_TARGETS_OF_HOXA9_AND_MEIS1_UP 0.001853683

BHATTACHARYA_EMBRYONIC_STEM_CELL 0.001853764

KEGG_GLYCINE_SERINE_AND_THREONINE_METABOLISM 0.00189834

REACTOME_SCFSKP2_MEDIATED_DEGRADATION_OF_P27_P21 0.0019027

CONCANNON_APOPTOSIS_BY_EPOXOMICIN_DN 0.001915947

HSIAO_HOUSEKEEPING_GENES 0.001929161

REACTOME_DNA_REPAIR 0.00192023

REACTOME_AUTODEGRADATION_OF_THE_E3_UBIQUITIN_LIGASE_COP1 0.00192005

REACTOME_CROSS_PRESENTATION_OF_SOLUBLE_EXOGENOUS_ANTIGENS_ENDOSOMES

0.001928601

WANG_TUMOR_INVASIVENESS_UP 0.002108976

GAVIN_FOXP3_TARGETS_CLUSTER_P6 0.002167866

WEST_ADRENOCORTICAL_TUMOR_UP 0.002239675

REACTOME_FORMATION_OF_THE_TERNARY_COMPLEX_AND_SUBSEQUENTLY_THE_43S_COMPLEX

0.002327348

REACTOME_TRANSCRIPTION_COUPLED_NER_TC_NER 0.002337969

REACTOME_RNA_POL_II_TRANSCRIPTION_PRE_INITIATION_AND_PROMOTER_OPENING 0.002420509

FERRANDO_T_ALL_WITH_MLL_ENL_FUSION_DN 0.002501969

ZHENG_GLIOBLASTOMA_PLASTICITY_UP 0.002678819

SENGUPTA_NASOPHARYNGEAL_CARCINOMA_UP 0.002762648

BOYAULT_LIVER_CANCER_SUBCLASS_G123_UP 0.002775263

MULLIGAN_NTF3_SIGNALING_VIA_INSR_AND_IGF1R_UP 0.002833347

REACTOME_NUCLEOTIDE_EXCISION_REPAIR 0.002912075

CUI_TCF21_TARGETS_2_UP 0.003046385

REACTOME_NEP_NS2_INTERACTS_WITH_THE_CELLULAR_EXPORT_MACHINERY 0.003041355

DAIRKEE_CANCER_PRONE_RESPONSE_BPA_E2 0.003028302

WU_APOPTOSIS_BY_CDKN1A_VIA_TP53 0.003156149

REACTOME_REGULATION_OF_GLUCOKINASE_BY_GLUCOKINASE_REGULATORY_PROTEIN

0.003198748

RAHMAN_TP53_TARGETS_PHOSPHORYLATED 0.00340997

REACTOME_RNA_POL_II_PRE_TRANSCRIPTION_EVENTS 0.003479256

SCHLOSSER_MYC_TARGETS_AND_SERUM_RESPONSE_UP 0.0036432

OUELLET_OVARIAN_CANCER_INVASIVE_VS_LMP_UP 0.003698932

SMID_BREAST_CANCER_LUMINAL_A_DN 0.003825309

SUNG_METASTASIS_STROMA_DN 0.003848299

RAMALHO_STEMNESS_UP 0.003851873

SANSOM_APC_TARGETS_REQUIRE_MYC 0.003859268

REACTOME_PEPTIDE_CHAIN_ELONGATION 0.003874295

SANA_RESPONSE_TO_IFNG_DN 0.003909009

REACTOME_GLUCOSE_TRANSPORT 0.004039369

REACTOME_CYTOSOLIC_TRNA_AMINOACYLATION 0.004060895

SU_TESTIS 0.004112674

KEGG_CITRATE_CYCLE_TCA_CYCLE 0.00414178

KIM_MYC_AMPLIFICATION_TARGETS_UP 0.004363033

REACTOME_REGULATION_OF_ORNITHINE_DECARBOXYLASE_ODC 0.004353139

LI_LUNG_CANCER 0.00441071

FINETTI_BREAST_CANCER_KINOME_RED 0.004635688

DUTERTRE_ESTRADIOL_RESPONSE_6HR_UP 0.004688067

VANDESLUIS_COMMD1_TARGETS_GROUP_3_UP 0.004698974

REACTOME_MRNA_3_END_PROCESSING 0.004691674

LI_WILMS_TUMOR_ANAPLASTIC_UP 0.004706814

KAUFFMANN_DNA_REPLICATION_GENES 0.004941855

SIMBULAN_PARP1_TARGETS_DN 0.004995643

BIOCARTA_PROTEASOME_PATHWAY 0.004983819

WELCSH_BRCA1_TARGETS_DN 0.00497569

BENPORATH_ES_2 0.005492686

KEGG_PYRIMIDINE_METABOLISM 0.005521932

NAKAMURA_TUMOR_ZONE_PERIPHERAL_VS_CENTRAL_UP 0.005826363

YU_BAP1_TARGETS 0.005840169

PID_BARD1_PATHWAY 0.006177565

COLLER_MYC_TARGETS_UP 0.006588799

STEIN_ESRRA_TARGETS_RESPONSIVE_TO_ESTROGEN_DN 0.006683783

MORI_SMALL_PRE_BII_LYMPHOCYTE_DN 0.006810769

GEORGES_CELL_CYCLE_MIR192_TARGETS 0.006796046

CHICAS_RB1_TARGETS_LOW_SERUM 0.006833628

WANG_CISPLATIN_RESPONSE_AND_XPC_UP 0.00682245

SAKAI_TUMOR_INFILTRATING_MONOCYTES_DN 0.006890627

SCHLOSSER_MYC_AND_SERUM_RESPONSE_SYNERGY 0.006872446

LY_AGING_MIDDLE_DN 0.006930432

IVANOVA_HEMATOPOIESIS_INTERMEDIATE_PROGENITOR 0.006922652

REACTOME_G1_S_SPECIFIC_TRANSCRIPTION 0.007061133

MOOTHA_PGC 0.007035733

CAFFAREL_RESPONSE_TO_THC_DN 0.007070926

XU_RESPONSE_TO_TRETINOIN_AND_NSC682994_DN 0.007076073

SLEBOS_HEAD_AND_NECK_CANCER_WITH_HPV_UP 0.007091065

REACTOME_METABOLISM_OF_NUCLEOTIDES 0.007276611

KEGG_CELL_CYCLE 0.008158214

KEGG_NUCLEOTIDE_EXCISION_REPAIR 0.008425525

KOINUMA_COLON_CANCER_MSI_UP 0.008432472

REACTOME_GLUCONEOGENESIS 0.008564906

SHEPARD_CRUSH_AND_BURN_MUTANT_DN 0.00872209

REACTOME_LAGGING_STRAND_SYNTHESIS 0.008977797

BROWN_MYELOID_CELL_DEVELOPMENT_DN 0.009018239

SCIAN_CELL_CYCLE_TARGETS_OF_TP53_AND_TP73_DN 0.009660927

BASSO_B_LYMPHOCYTE_NETWORK 0.009741358

BIOCARTA_MCM_PATHWAY 0.0097145

MILI_PSEUDOPODIA_HAPTOTAXIS_UP 0.00991022

LI_DCP2_BOUND_MRNA 0.009905435

MATTIOLI_MGUS_VS_PCL 0.010136875

EPPERT_PROGENITOR 0.010118507

SPIELMAN_LYMPHOBLAST_EUROPEAN_VS_ASIAN_UP 0.010510278

REACTOME_P53_DEPENDENT_G1_DNA_DAMAGE_RESPONSE 0.010960286

HU_ANGIOGENESIS_DN 0.011277007

VIETOR_IFRD1_TARGETS 0.011293047

PODAR_RESPONSE_TO_ADAPHOSTIN_DN 0.01155716

YAMAZAKI_TCEB3_TARGETS_DN 0.011700117

REACTOME_SIGNALING_BY_WNT 0.012041292

REACTOME_GLOBAL_GENOMIC_NER_GG_NER 0.012166548

REACTOME_REGULATION_OF_APOPTOSIS 0.012411093

MORI_PRE_BI_LYMPHOCYTE_UP 0.01324017

ONDER_CDH1_TARGETS_1_DN 0.013365828

REACTOME_FORMATION_OF_THE_HIV1_EARLY_ELONGATION_COMPLEX 0.013598256

WONG_PROTEASOME_GENE_MODULE 0.013636219

SHEPARD_BMYB_TARGETS 0.013622595

REACTOME_MRNA_CAPPING 0.013742478

ZHONG_SECRETOME_OF_LUNG_CANCER_AND_ENDOTHELIUM 0.014749183

CHEN_ETV5_TARGETS_TESTIS 0.014907429

MORI_EMU_MYC_LYMPHOMA_BY_ONSET_TIME_UP 0.01585409

PYEON_CANCER_HEAD_AND_NECK_VS_CERVICAL_UP 0.015951287

LY_AGING_PREMATURE_DN 0.016542112

REACTOME_FANCONI_ANEMIA_PATHWAY 0.01658848

REACTOME_PYRUVATE_METABOLISM_AND_CITRIC_ACID_TCA_CYCLE 0.017212767

XU_HGF_SIGNALING_NOT_VIA_AKT1_48HR_DN 0.017300528

REACTOME_HOMOLOGOUS_RECOMBINATION_REPAIR_OF_REPLICATION_INDEPENDENT_DOUBLE_STRAND_BREAKS

0.017632818

KAUFFMANN_DNA_REPAIR_GENES 0.017775988

ELVIDGE_HYPOXIA_DN 0.017940542

REACTOME_DESTABILIZATION_OF_MRNA_BY_KSRP 0.019698039

TIEN_INTESTINE_PROBIOTICS_6HR_UP 0.019642957

KEGG_PURINE_METABOLISM 0.02097551

MODY_HIPPOCAMPUS_PRENATAL 0.021093989

REACTOME_FORMATION_OF_RNA_POL_II_ELONGATION_COMPLEX_ 0.021630451

REACTOME_G0_AND_EARLY_G1 0.021584554

KEGG_RNA_POLYMERASE 0.022233676

APPIERTO_RESPONSE_TO_FENRETINIDE_DN 0.02248662

REACTOME_ACYL_CHAIN_REMODELLING_OF_PG 0.022501333

REACTOME_ABORTIVE_ELONGATION_OF_HIV1_TRANSCRIPT_IN_THE_ABSENCE_OF_TAT

0.022882931

IVANOVA_HEMATOPOIESIS_EARLY_PROGENITOR 0.022983784

LEE_METASTASIS_AND_RNA_PROCESSING_UP 0.02312138

KEGG_ALZHEIMERS_DISEASE 0.023139939

REACTOME_DEADENYLATION_DEPENDENT_MRNA_DECAY 0.023276055

GRADE_METASTASIS_DN 0.023248803

ACOSTA_PROLIFERATION_INDEPENDENT_MYC_TARGETS_UP 0.02320237

LIANG_HEMATOPOIESIS_STEM_CELL_NUMBER_LARGE_VS_TINY_UP 0.024126679

BOHN_PRIMARY_IMMUNODEFICIENCY_SYNDROM_UP 0.024080604

REACTOME_ER_PHAGOSOME_PATHWAY 0.024212316

REACTOME_CHOLESTEROL_BIOSYNTHESIS 0.024825582

ZHONG_SECRETOME_OF_LUNG_CANCER_AND_MACROPHAGE 0.024808092

HU_GENOTOXIC_DAMAGE_4HR 0.024793582

KEGG_HOMOLOGOUS_RECOMBINATION 0.025340173

YAO_TEMPORAL_RESPONSE_TO_PROGESTERONE_CLUSTER_8 0.025779434

BURTON_ADIPOGENESIS_4 0.025931334

BOYAULT_LIVER_CANCER_SUBCLASS_G23_UP 0.026327047

DELPUECH_FOXO3_TARGETS_DN 0.026555032

REACTOME_PROCESSING_OF_CAPPED_INTRONLESS_PRE_MRNA 0.026659565

HEDENFALK_BREAST_CANCER_BRCA1_VS_BRCA2 0.027054107

CAIRO_PML_TARGETS_BOUND_BY_MYC_UP 0.026998844

KEGG_MISMATCH_REPAIR 0.028006114

KEGG_RNA_DEGRADATION 0.028049294

AMIT_SERUM_RESPONSE_480_MCF10A 0.028230725

REACTOME_APC_CDC20_MEDIATED_DEGRADATION_OF_NEK2A 0.02818035

REACTOME_ACTIVATION_OF_NF_KAPPAB_IN_B_CELLS 0.028162064

HUANG_GATA2_TARGETS_DN 0.028170647

ENK_UV_RESPONSE_KERATINOCYTE_DN 0.028972268

ROME_INSULIN_TARGETS_IN_MUSCLE_UP 0.028902218

MOREIRA_RESPONSE_TO_TSA_UP 0.028877307

ZHAN_MULTIPLE_MYELOMA_SUBGROUPS 0.0297069

ELVIDGE_HIF1A_TARGETS_UP 0.02977637

HWANG_PROSTATE_CANCER_MARKERS 0.030057088

CHNG_MULTIPLE_MYELOMA_HYPERPLOID_UP 0.030986125

MARTINEZ_RESPONSE_TO_TRABECTEDIN_DN 0.031004503

GARGALOVIC_RESPONSE_TO_OXIDIZED_PHOSPHOLIPIDS_TURQUOISE_DN 0.03116907

SESTO_RESPONSE_TO_UV_C7 0.031583533

REACTOME_PREFOLDIN_MEDIATED_TRANSFER_OF_SUBSTRATE_TO_CCT_TRIC 0.031533767

CHEN_HOXA5_TARGETS_9HR_DN 0.03162939

REACTOME_MITOCHONDRIAL_TRNA_AMINOACYLATION 0.03155171

IWANAGA_E2F1_TARGETS_INDUCED_BY_SERUM 0.03177377

SHAFFER_IRF4_TARGETS_IN_ACTIVATED_B_LYMPHOCYTE 0.031723853

WHITFIELD_CELL_CYCLE_G2_M 0.032164063

LI_WILMS_TUMOR_VS_FETAL_KIDNEY_2_UP 0.03229004

RAY_TUMORIGENESIS_BY_ERBB2_CDC25A_UP 0.032269157

STEIN_ESRRA_TARGETS_UP 0.032383967

REACTOME_PROCESSIVE_SYNTHESIS_ON_THE_LAGGING_STRAND 0.032595444

REACTOME_CITRIC_ACID_CYCLE_TCA_CYCLE 0.033134826

DAIRKEE_TERT_TARGETS_UP 0.033323143

MONNIER_POSTRADIATION_TUMOR_ESCAPE_UP 0.033450596

PID_ATM_PATHWAY 0.03422855

STEIN_ESR1_TARGETS 0.03418846

SANSOM_APC_TARGETS_UP 0.034258876

REACTOME_INHIBITION_OF_THE_PROTEOLYTIC_ACTIVITY_OF_APC_C_REQUIRED_FOR_THE_ONSET_OF_ANAPHASE_BY_MITOTIC_SPINDLE_CHECKPOINT_COMPONENTS

0.034713715

RIZ_ERYTHROID_DIFFERENTIATION 0.034689855

HORTON_SREBF_TARGETS 0.034617167

WEST_ADRENOCORTICAL_CARCINOMA_VS_ADENOMA_UP 0.034645244

REACTOME_LIPID_DIGESTION_MOBILIZATION_AND_TRANSPORT 0.03457555

WAKASUGI_HAVE_ZNF143_BINDING_SITES 0.034545302

SHEPARD_CRUSH_AND_BURN_MUTANT_UP 0.035008907

REACTOME_FORMATION_OF_TUBULIN_FOLDING_INTERMEDIATES_BY_CCT_TRIC 0.0353697

REACTOME_ANTIGEN_PROCESSING_CROSS_PRESENTATION 0.035667773

PEART_HDAC_PROLIFERATION_CLUSTER_DN 0.035799976

REACTOME_METABOLISM_OF_CARBOHYDRATES 0.03586938

REACTOME_TRANSCRIPTION 0.03581211

ZEMBUTSU_SENSITIVITY_TO_METHOTREXATE 0.03594765

REACTOME_CHROMOSOME_MAINTENANCE 0.035878576

REACTOME_MICRORNA_MIRNA_BIOGENESIS 0.035842936

MIKKELSEN_IPS_ICP_WITH_H3K27ME3 0.035823833

WIERENGA_PML_INTERACTOME 0.035896767

LI_AMPLIFIED_IN_LUNG_CANCER 0.036037393

JIANG_AGING_CEREBRAL_CORTEX_DN 0.036270954

JACKSON_DNMT1_TARGETS_DN 0.036188204

CHIARADONNA_NEOPLASTIC_TRANSFORMATION_KRAS_UP 0.036166318

JIANG_HYPOXIA_VIA_VHL 0.036712542

XU_HGF_TARGETS_INDUCED_BY_AKT1_48HR_DN 0.036742643

KEGG_TERPENOID_BACKBONE_BIOSYNTHESIS 0.037361898

KIM_WT1_TARGETS_DN 0.038175456

MOOTHA_GLUCONEOGENESIS 0.038779676

YAMASHITA_LIVER_CANCER_WITH_EPCAM_UP 0.038705867

HONMA_DOCETAXEL_RESISTANCE 0.039003097

MARKEY_RB1_CHRONIC_LOF_UP 0.038942944

TSENG_IRS1_TARGETS_UP 0.039040554

WHITFIELD_CELL_CYCLE_G2 0.039069243

KEGG_ONE_CARBON_POOL_BY_FOLATE 0.039880928

REACTOME_METABOLISM_OF_AMINO_ACIDS_AND_DERIVATIVES 0.04056944

KEGG_BASAL_TRANSCRIPTION_FACTORS 0.040689286

WANG_METASTASIS_OF_BREAST_CANCER_ESR1_UP 0.04095919

REACTOME_GLUCOSE_METABOLISM 0.041070715

PUJANA_BREAST_CANCER_LIT_INT_NETWORK 0.041143205

TONKS_TARGETS_OF_RUNX1_RUNX1T1_FUSION_MONOCYTE_UP 0.041851487

REACTOME_ELONGATION_ARREST_AND_RECOVERY 0.042004857

SANSOM_APC_TARGETS 0.0419946

JIANG_AGING_HYPOTHALAMUS_UP 0.042091217

REACTOME_FORMATION_OF_TRANSCRIPTION_COUPLED_NER_TC_NER_REPAIR_COMPLEX

0.04232191

WANG_SMARCE1_TARGETS_DN 0.043018315

FOURNIER_ACINAR_DEVELOPMENT_LATE_DN 0.043357648

MOOTHA_TCA 0.043804713

REACTOME_APC_C_CDC20_MEDIATED_DEGRADATION_OF_CYCLIN_B 0.04405759

KIM_WT1_TARGETS_12HR_DN 0.044231188

KEGG_PENTOSE_PHOSPHATE_PATHWAY 0.044490688

REACTOME_RNA_POL_III_TRANSCRIPTION_INITIATION_FROM_TYPE_2_PROMOTER 0.04467144

ZHAN_MULTIPLE_MYELOMA_CD2_DN 0.04464282

REACTOME_PHOSPHORYLATION_OF_THE_APC_C 0.04474921

MODY_HIPPOCAMPUS_NEONATAL 0.04488017

VANTVEER_BREAST_CANCER_POOR_PROGNOSIS 0.045402046

ZHONG_SECRETOME_OF_LUNG_CANCER_AND_FIBROBLAST 0.046068456

BILANGES_SERUM_AND_RAPAMYCIN_SENSITIVE_GENES 0.0469285

REACTOME_GLYCOLYSIS 0.04718064

REACTOME_RNA_POL_III_TRANSCRIPTION 0.047572095

GROSS_HYPOXIA_VIA_ELK3_AND_HIF1A_DN 0.047473013

WANG_RESPONSE_TO_BEXAROTENE_UP 0.047821827

JAIN_NFKB_SIGNALING 0.04780573

BIOCARTA_ATRBRCA_PATHWAY 0.047897663

REACTOME_RNA_POL_I_TRANSCRIPTION_TERMINATION 0.048110947

MOHANKUMAR_TLX1_TARGETS_UP 0.04815335

MARTORIATI_MDM4_TARGETS_FETAL_LIVER_UP 0.04945574

Supplementary Table S9. Gene sets down-regulated in SHP2-deficient, compared with SHP2-replete, WT pre-B cells.

NAME FDR q-val

KEGG_SYSTEMIC_LUPUS_ERYTHEMATOSUS 0

REACTOME_MEIOTIC_RECOMBINATION 0

REACTOME_RNA_POL_I_TRANSCRIPTION 0

REACTOME_RNA_POL_I_RNA_POL_III_AND_MITOCHONDRIAL_TRANSCRIPTION 0

REACTOME_RNA_POL_I_PROMOTER_OPENING 0

REACTOME_AMYLOIDS 0

REACTOME_PACKAGING_OF_TELOMERE_ENDS 0

REACTOME_MEIOSIS 0

REACTOME_TELOMERE_MAINTENANCE 0

REACTOME_DEPOSITION_OF_NEW_CENPA_CONTAINING_NUCLEOSOMES_AT_THE_CENTROMERE

3.32E-04

REACTOME_TRANSCRIPTION 3.02E-04

MANALO_HYPOXIA_DN 4.85E-04

REACTOME_MEIOTIC_SYNAPSIS 7.71E-04

ACEVEDO_LIVER_CANCER_WITH_H3K9ME3_DN 0.002988548

REACTOME_CHROMOSOME_MAINTENANCE 0.005174248

STEIN_ESRRA_TARGETS_RESPONSIVE_TO_ESTROGEN_UP 0.005004874

WILLIAMS_ESR1_TARGETS_UP 0.018655982

REACTOME_RESPIRATORY_ELECTRON_TRANSPORT 0.033274826

TONKS_TARGETS_OF_RUNX1_RUNX1T1_FUSION_SUSTAINED_IN_MONOCYTE_UP 0.03742117

ACEVEDO_LIVER_CANCER_WITH_H3K27ME3_DN 0.046772476

REACTOME_RESPIRATORY_ELECTRON_TRANSPORT_ATP_SYNTHESIS_BY_CHEMIOSMOTIC_COUPLING_AND_HEAT_PRODUCTION_BY_UNCOUPLING_PROTEINS_

0.0467156

REACTOME_FORMATION_OF_TRANSCRIPTION_COUPLED_NER_TC_NER_REPAIR_COMPLEX

0.0478413

Supplementary Table S10. Gene sets up-regulated in SHP2-deficient, compared with SHP2-replete, BCR-ABL1+ pre-B cells.

NAME FDR q-val

REACTOME_AMYLOIDS 0

REACTOME_RNA_POL_I_PROMOTER_OPENING 0

KEGG_SYSTEMIC_LUPUS_ERYTHEMATOSUS 0

RADAEVA_RESPONSE_TO_IFNA1_UP 0

LIU_VAV3_PROSTATE_CARCINOGENESIS_UP 0

REACTOME_PACKAGING_OF_TELOMERE_ENDS 0

KRASNOSELSKAYA_ILF3_TARGETS_UP 0

BROWNE_INTERFERON_RESPONSIVE_GENES 1.73E-04

KOBAYASHI_EGFR_SIGNALING_24HR_UP 1.54E-04

REACTOME_MEIOTIC_SYNAPSIS 1.39E-04

MOSERLE_IFNA_RESPONSE 1.26E-04

LEE_LIVER_CANCER_E2F1_UP 1.16E-04

DAUER_STAT3_TARGETS_DN 1.07E-04

MARKEY_RB1_ACUTE_LOF_DN 9.91E-05

WIELAND_UP_BY_HBV_INFECTION 9.25E-05

ICHIBA_GRAFT_VERSUS_HOST_DISEASE_D7_UP 8.67E-05

REACTOME_INTERFERON_ALPHA_BETA_SIGNALING 1.65E-04

REACTOME_MEIOTIC_RECOMBINATION 1.56E-04

EINAV_INTERFERON_SIGNATURE_IN_CANCER 1.48E-04

BENNETT_SYSTEMIC_LUPUS_ERYTHEMATOSUS 1.41E-04

DIAZ_CHRONIC_MEYLOGENOUS_LEUKEMIA_DN 1.34E-04

REACTOME_MEIOSIS 1.92E-04

LEE_LIVER_CANCER_MYC_E2F1_UP 1.83E-04

STAMBOLSKY_TARGETS_OF_MUTATED_TP53_DN 1.76E-04

REACTOME_TELOMERE_MAINTENANCE 2.22E-04

LEE_LIVER_CANCER_DENA_UP 3.19E-04

WANG_CLASSIC_ADIPOGENIC_TARGETS_OF_PPARG 3.58E-04

REACTOME_RNA_POL_I_TRANSCRIPTION 3.45E-04

BOYLAN_MULTIPLE_MYELOMA_PCA3_DN 3.80E-04

STEARMAN_TUMOR_FIELD_EFFECT_UP 5.49E-04

BORLAK_LIVER_CANCER_EGF_UP 5.32E-04

NIELSEN_GIST_AND_SYNOVIAL_SARCOMA_DN 5.15E-04

LIAN_LIPA_TARGETS_6M 5.00E-04

ICHIBA_GRAFT_VERSUS_HOST_DISEASE_35D_UP 4.85E-04

ZHANG_INTERFERON_RESPONSE 4.71E-04

APPEL_IMATINIB_RESPONSE 4.96E-04

HELLER_SILENCED_BY_METHYLATION_UP 5.92E-04

LINDSTEDT_DENDRITIC_CELL_MATURATION_B 6.50E-04

BOYLAN_MULTIPLE_MYELOMA_D_DN 6.33E-04

KIM_GLIS2_TARGETS_UP 6.84E-04

ALTEMEIER_RESPONSE_TO_LPS_WITH_MECHANICAL_VENTILATION 7.99E-04

ZHANG_TLX_TARGETS_36HR_UP 7.80E-04

BROWNE_HCMV_INFECTION_30MIN_UP 8.56E-04

HESS_TARGETS_OF_HOXA9_AND_MEIS1_DN 8.67E-04

VALK_AML_CLUSTER_5 9.37E-04

LIAN_LIPA_TARGETS_3M 0.001006884

PARK_APL_PATHOGENESIS_DN 0.001217072

STEARMAN_LUNG_CANCER_EARLY_VS_LATE_DN 0.001337456

LEE_LIVER_CANCER_CIPROFIBRATE_UP 0.001338276

MORI_MATURE_B_LYMPHOCYTE_DN 0.001446784

TIAN_TNF_SIGNALING_VIA_NFKB 0.001499085

ZHENG_GLIOBLASTOMA_PLASTICITY_DN 0.001549072

BOYLAN_MULTIPLE_MYELOMA_D_CLUSTER_DN 0.001519844

WUNDER_INFLAMMATORY_RESPONSE_AND_CHOLESTEROL_UP 0.00166759

ZHANG_TLX_TARGETS_UP 0.001761388

GUENTHER_GROWTH_SPHERICAL_VS_ADHERENT_DN 0.00197151

BOSCO_INTERFERON_INDUCED_ANTIVIRAL_MODULE 0.002797873

RAMALHO_STEMNESS_DN 0.003216282

JISON_SICKLE_CELL_DISEASE_UP 0.003763037

REACTOME_RNA_POL_I_RNA_POL_III_AND_MITOCHONDRIAL_TRANSCRIPTION 0.003925252

NIELSEN_SYNOVIAL_SARCOMA_DN 0.003948669

DORN_ADENOVIRUS_INFECTION_24HR_DN 0.00395029

UROSEVIC_RESPONSE_TO_IMIQUIMOD 0.004452196

HELLER_HDAC_TARGETS_UP 0.004742985

ZHANG_TLX_TARGETS_60HR_UP 0.005216428

NAKAYAMA_SOFT_TISSUE_TUMORS_PCA1_UP 0.005157406

KHETCHOUMIAN_TRIM24_TARGETS_UP 0.005121127

PID_PTP1B_PATHWAY 0.005146057

SATO_SILENCED_BY_DEACETYLATION_IN_PANCREATIC_CANCER 0.0052866

DORN_ADENOVIRUS_INFECTION_12HR_UP 0.005211077

LEE_LIVER_CANCER_ACOX1_UP 0.005405729

BROWN_MYELOID_CELL_DEVELOPMENT_UP 0.005955741

KINSEY_TARGETS_OF_EWSR1_FLII_FUSION_DN 0.00617404

DER_IFN_GAMMA_RESPONSE_UP 0.006235128

MISSIAGLIA_REGULATED_BY_METHYLATION_UP 0.006151993

VERHAAK_GLIOBLASTOMA_MESENCHYMAL 0.00723675

KIM_LRRC3B_TARGETS 0.007340145

DER_IFN_ALPHA_RESPONSE_UP 0.007246041

NADLER_OBESITY_UP 0.008501624

REACTOME_DEPOSITION_OF_NEW_CENPA_CONTAINING_NUCLEOSOMES_AT_THE_CENTROMERE

0.008817456

REACTOME_INTERFERON_GAMMA_SIGNALING 0.008776232

TAKEDA_TARGETS_OF_NUP98_HOXA9_FUSION_6HR_DN 0.009734066

OLSSON_E2F3_TARGETS_DN 0.01043646

GAJATE_RESPONSE_TO_TRABECTEDIN_UP 0.010440354

VALK_AML_WITH_FLT3_ITD 0.011272837

MASRI_RESISTANCE_TO_TAMOXIFEN_AND_AROMATASE_INHIBITORS_DN 0.011459511

HINATA_NFKB_TARGETS_KERATINOCYTE_UP 0.011374603

SEKI_INFLAMMATORY_RESPONSE_LPS_DN 0.011710878

SAKAI_CHRONIC_HEPATITIS_VS_LIVER_CANCER_DN 0.011915324

FERREIRA_EWINGS_SARCOMA_UNSTABLE_VS_STABLE_DN 0.011828718

ZHANG_ANTIVIRAL_RESPONSE_TO_RIBAVIRIN_UP 0.011713286

ZHONG_RESPONSE_TO_AZACITIDINE_AND_TSA_UP 0.012194741

MIKKELSEN_MCV6_LCP_WITH_H3K4ME3 0.012166575

SANA_TNF_SIGNALING_UP 0.012456598

FURUKAWA_DUSP6_TARGETS_PCI35_UP 0.012511921

REACTOME_CHROMOSOME_MAINTENANCE 0.014318254

BOYAULT_LIVER_CANCER_SUBCLASS_G5_DN 0.014213107

GRANDVAUX_IRF3_TARGETS_UP 0.014831552

MARKEY_RB1_CHRONIC_LOF_DN 0.015161894

GRAESSMANN_RESPONSE_TO_MC_AND_SERUM_DEPRIVATION_UP 0.015051561

DEMAGALHAES_AGING_UP 0.014902535

LINDGREN_BLADDER_CANCER_HIGH_RECURRENCE 0.015130105

SERVITJA_LIVER_HNF1A_TARGETS_UP 0.016083304

HELLEBREKERS_SILENCED_DURING_TUMOR_ANGIOGENESIS 0.01609735

JECHLINGER_EPITHELIAL_TO_MESENCHYMAL_TRANSITION_UP 0.01638458

JOHNSTONE_PARVB_TARGETS_3_UP 0.016613165

OHGUCHI_LIVER_HNF4A_TARGETS_UP 0.016647913

KOHOUTEK_CCNT1_TARGETS 0.019042728

BURTON_ADIPOGENESIS_PEAK_AT_0HR 0.020083403

FRIDMAN_SENESCENCE_UP 0.020135893

ZHANG_RESPONSE_TO_IKK_INHIBITOR_AND_TNF_UP 0.020298384

CROONQUIST_STROMAL_STIMULATION_UP 0.020824013

TARTE_PLASMA_CELL_VS_PLASMABLAST_UP 0.021769157

PID_INTEGRIN_A9B1_PATHWAY 0.021852786

GALINDO_IMMUNE_RESPONSE_TO_ENTEROTOXIN 0.022787087

SEITZ_NEOPLASTIC_TRANSFORMATION_BY_8P_DELETION_UP 0.02310828

NOJIMA_SFRP2_TARGETS_DN 0.023564564

ABRAHAM_ALPC_VS_MULTIPLE_MYELOMA_UP 0.023548057

TAKEDA_TARGETS_OF_NUP98_HOXA9_FUSION_3D_UP 0.023396166

AMIT_EGF_RESPONSE_240_MCF10A 0.023687514

GOLUB_ALL_VS_AML_DN 0.024987454

MURAKAMI_UV_RESPONSE_6HR_UP 0.025039628

RASHI_RESPONSE_TO_IONIZING_RADIATION_2 0.0253924

ROY_WOUND_BLOOD_VESSEL_UP 0.025835332

REACTOME_CYTOKINE_SIGNALING_IN_IMMUNE_SYSTEM 0.025956415

REACTOME_INTERFERON_SIGNALING 0.02617028

FULCHER_INFLAMMATORY_RESPONSE_LECTIN_VS_LPS_DN 0.026308049

KAMIKUBO_MYELOID_CEBPA_NETWORK 0.026102519

GERHOLD_ADIPOGENESIS_UP 0.026047817

WIEDERSCHAIN_TARGETS_OF_BMI1_AND_PCGF2 0.025963832

REACTOME_RIP_MEDIATED_NFKB_ACTIVATION_VIA_DAI 0.026004009

PARK_TRETINOIN_RESPONSE_AND_PML_RARA_FUSION 0.026085151

TAKEDA_TARGETS_OF_NUP98_HOXA9_FUSION_8D_DN 0.026000982

TSAI_RESPONSE_TO_RADIATION_THERAPY 0.026902892

DACOSTA_UV_RESPONSE_VIA_ERCC3_COMMON_UP 0.027301565

HELLER_HDAC_TARGETS_SILENCED_BY_METHYLATION_UP 0.027703345

HAN_JNK_SINGALING_DN 0.027930992

KRIEG_HYPOXIA_VIA_KDM3A 0.028017256

VERHAAK_AML_WITH_NPM1_MUTATED_UP 0.028128674

ANASTASSIOU_CANCER_MESENCHYMAL_TRANSITION_SIGNATURE 0.027975481

LEE_LIVER_CANCER_MYC_TGFA_UP 0.0283661

SHIN_B_CELL_LYMPHOMA_CLUSTER_8 0.028346566

REACTOME_TRAF6_MEDIATED_NFKB_ACTIVATION 0.028502483

URS_ADIPOCYTE_DIFFERENTIATION_UP 0.028597908

REACTOME_MHC_CLASS_II_ANTIGEN_PRESENTATION 0.028437614

HERNANDEZ_MITOTIC_ARREST_BY_DOCETAXEL_1_UP 0.029014837

CHIBA_RESPONSE_TO_TSA 0.029574696

PID_INTEGRIN1_PATHWAY 0.030112093

MCDOWELL_ACUTE_LUNG_INJURY_UP 0.030148184

XU_RESPONSE_TO_TRETINOIN_AND_NSC682994_UP 0.03176392

SUH_COEXPRESSED_WITH_ID1_AND_ID2_UP 0.033264264

COLIN_PILOCYTIC_ASTROCYTOMA_VS_GLIOBLASTOMA_DN 0.033054117

PEREZ_TP53_AND_TP63_TARGETS 0.032865047

WANG_BARRETTS_ESOPHAGUS_DN 0.032882314

BERENJENO_TRANSFORMED_BY_RHOA_DN 0.032888368

LEE_AGING_CEREBELLUM_UP 0.033645816

JUBAN_TARGETS_OF_SPI1_AND_FLI1_UP 0.034676794

LIEN_BREAST_CARCINOMA_METAPLASTIC 0.034800723

CASTELLANO_NRAS_TARGETS_UP 0.034769434

ROSS_AML_WITH_MLL_FUSIONS 0.034740396

RODWELL_AGING_KIDNEY_UP 0.03703404

ABBUD_LIF_SIGNALING_1_UP 0.03797954

TAKEDA_TARGETS_OF_NUP98_HOXA9_FUSION_10D_DN 0.038719926

LIN_APC_TARGETS 0.038617156

WELCH_GATA1_TARGETS 0.038621325

SESTO_RESPONSE_TO_UV_C4 0.038446333

LIU_SMARCA4_TARGETS 0.038240492

LIANG_SILENCED_BY_METHYLATION_2 0.038135275

SARRIO_EPITHELIAL_MESENCHYMAL_TRANSITION_DN 0.038417153

YANG_MUC2_TARGETS_DUODENUM_3MO_DN 0.039514486

DAZARD_UV_RESPONSE_CLUSTER_G2 0.040148877

WILENSKY_RESPONSE_TO_DARAPLADIB 0.040865306

DACOSTA_ERCC3_ALLELE_XPCS_VS_TTD_UP 0.04145488

BIOCARTA_NKT_PATHWAY 0.04216871

NABA_ECM_REGULATORS 0.043314558

MAHAJAN_RESPONSE_TO_IL1A_UP 0.043168508

GUILLAUMOND_KLF10_TARGETS_UP 0.043563344

KEGG_LYSOSOME 0.04384237

REACTOME_CHEMOKINE_RECEPTORS_BIND_CHEMOKINES 0.04436534

FONTAINE_THYROID_TUMOR_UNCERTAIN_MALIGNANCY_DN 0.0441339

DELLA_RESPONSE_TO_TSA_AND_BUTYRATE 0.044175774

CHIBA_RESPONSE_TO_TSA_UP 0.043947928

FRASOR_RESPONSE_TO_ESTRADIOL_DN 0.043722507

SCHOEN_NFKB_SIGNALING 0.043663893

NABA_ECM_AFFILIATED 0.045240484

KEGG_PRIMARY_IMMUNODEFICIENCY 0.04549048

GERY_CEBP_TARGETS 0.04563397

VARELA_ZMPSTE24_TARGETS_UP 0.04542035

MEISSNER_BRAIN_HCP_WITH_H3K4ME2_AND_H3K27ME3 0.04580047

WESTON_VEGFA_TARGETS_3HR 0.045873426

KEGG_PPAR_SIGNALING_PATHWAY 0.04690417

SEKI_INFLAMMATORY_RESPONSE_LPS_UP 0.04830777

LEIN_ASTROCYTE_MARKERS 0.048573136

KEGG_NICOTINATE_AND_NICOTINAMIDE_METABOLISM 0.049012605

Supplementary Table S11. Gene sets up-regulated in SHP2-deficient, compared with SHP2-replete, WT pre-B cells.

NAME FDR q-val

LEONARD_HYPOXIA 0

QI_HYPOXIA 0

FARDIN_HYPOXIA_11 0

ELVIDGE_HYPOXIA_BY_DMOG_UP 0

ELVIDGE_HIF1A_AND_HIF2A_TARGETS_DN 0

MENSE_HYPOXIA_UP 0

ELVIDGE_HYPOXIA_UP 0

KEGG_GLYCOLYSIS_GLUCONEOGENESIS 0

WANG_ADIPOGENIC_GENES_REPRESSED_BY_SIRT1 0

ELVIDGE_HIF1A_TARGETS_DN 0

SEMENZA_HIF1_TARGETS 0

SCHMIDT_POR_TARGETS_IN_LIMB_BUD_UP 0

KIM_HYPOXIA 0

MORI_PRE_BI_LYMPHOCYTE_DN 0

GROSS_HYPOXIA_VIA_ELK3_AND_HIF1A_UP 0

VANDESLUIS_COMMD1_TARGETS_GROUP_3_UP 0

HARRIS_HYPOXIA 0

MAINA_VHL_TARGETS_DN 1.18E-04

YU_MYC_TARGETS_DN 2.24E-04

REACTOME_GLUCOSE_METABOLISM 2.67E-04

KRIGE_AMINO_ACID_DEPRIVATION 6.62E-04

GROSS_ELK3_TARGETS_DN 6.32E-04

PID_HIF1_TFPATHWAY 6.04E-04

KUROZUMI_RESPONSE_TO_ONCOCYTIC_VIRUS 6.24E-04

ZHAN_MULTIPLE_MYELOMA_CD1_VS_CD2_UP 8.12E-04

GRABARCZYK_BCL11B_TARGETS_UP 9.03E-04

KAN_RESPONSE_TO_ARSENIC_TRIOXIDE 0.001027934

MARKEY_RB1_ACUTE_LOF_DN 9.91E-04

REACTOME_GLYCOLYSIS 0.001104998

REACTOME_CHOLESTEROL_BIOSYNTHESIS 0.001281573

WINTER_HYPOXIA_METAGENE 0.001240232

PRAMOONJAGO_SOX4_TARGETS_UP 0.001468657

PODAR_RESPONSE_TO_ADAPHOSTIN_UP 0.002037634

MANALO_HYPOXIA_UP 0.00301506

MOOTHA_GLUCONEOGENESIS 0.003172523

MOOTHA_GLYCOLYSIS 0.003824294

KEGG_FRUCTOSE_AND_MANNOSE_METABOLISM 0.003979231

KUROZUMI_RESPONSE_TO_ONCOCYTIC_VIRUS_AND_CYCLIC_RGD 0.004042801

HORTON_SREBF_TARGETS 0.004701823

MORI_LARGE_PRE_BII_LYMPHOCYTE_DN 0.004664054

JIANG_HYPOXIA_NORMAL 0.005357084

SCHAEFFER_PROSTATE_DEVELOPMENT_12HR_UP 0.005279935

OSWALD_HEMATOPOIETIC_STEM_CELL_IN_COLLAGEN_GEL_DN 0.005604145

REACTOME_GLUCONEOGENESIS 0.005960182

LUI_THYROID_CANCER_CLUSTER_2 0.006157725

WINTER_HYPOXIA_UP 0.006907697

BRACHAT_RESPONSE_TO_METHOTREXATE_DN 0.006783071

KEGG_PENTOSE_PHOSPHATE_PATHWAY 0.006998581

OXFORD_RALA_OR_RALB_TARGETS_DN 0.007008196

GROSS_HIF1A_TARGETS_DN 0.007294639

BRUNO_HEMATOPOIESIS 0.007610428

REACTOME_PYRUVATE_METABOLISM 0.007730594

MARTORIATI_MDM4_TARGETS_FETAL_LIVER_UP 0.007724608

GAJATE_RESPONSE_TO_TRABECTEDIN_UP 0.00758156

CHANG_CORE_SERUM_RESPONSE_DN 0.007657066

REACTOME_PYRUVATE_METABOLISM_AND_CITRIC_ACID_TCA_CYCLE 0.008223914

GARY_CD5_TARGETS_UP 0.008379368

GAUSSMANN_MLL_AF4_FUSION_TARGETS_E_DN 0.008326657

KEGG_PYRUVATE_METABOLISM 0.008203487

QI_HYPOXIA_TARGETS_OF_HIF1A_AND_FOXA2 0.008563616

MARCHINI_TRABECTEDIN_RESISTANCE_DN 0.01066163

REACTOME_ION_TRANSPORT_BY_P_TYPE_ATPASES 0.011402122

KASLER_HDAC7_TARGETS_2_DN 0.013236957

FUJII_YBX1_TARGETS_UP 0.013428448

ZHAN_MULTIPLE_MYELOMA_CD1_UP 0.01395925

YAO_TEMPORAL_RESPONSE_TO_PROGESTERONE_CLUSTER_0 0.015994133

KARLSSON_TGFB1_TARGETS_DN 0.015882947

RUIZ_TNC_TARGETS_UP 0.016902603

PAPASPYRIDONOS_UNSTABLE_ATEROSCLEROTIC_PLAQUE_DN 0.016719284

BERENJENO_TRANSFORMED_BY_RHOA_DN 0.019675063

REACTOME_ION_CHANNEL_TRANSPORT 0.020177819

GARGALOVIC_RESPONSE_TO_OXIDIZED_PHOSPHOLIPIDS_RED_UP 0.020400068

PENG_LEUCINE_DEPRIVATION_UP 0.020704133

SMIRNOV_RESPONSE_TO_IR_6HR_DN 0.0215768

ONO_AML1_TARGETS_DN 0.022397919

YANAGIHARA_ESX1_TARGETS 0.022636447

REACTOME_ANTIGEN_ACTIVATES_B_CELL_RECEPTOR_LEADING_TO_GENERATION_OF_SECOND_MESSENGERS

0.022924025

BRACHAT_RESPONSE_TO_CAMPTOTHECIN_DN 0.02282082

BAE_BRCA1_TARGETS_UP 0.023273768

GEISS_RESPONSE_TO_DSRNA_UP 0.023995353

TORCHIA_TARGETS_OF_EWSR1_FLI1_FUSION_UP 0.023804028

MARTORIATI_MDM4_TARGETS_NEUROEPITHELIUM_UP 0.026424088

IKEDA_MIR133_TARGETS_UP 0.02633643

ONDER_CDH1_SIGNALING_VIA_CTNNB1 0.026035374

LEE_DIFFERENTIATING_T_LYMPHOCYTE 0.026080225

WEINMANN_ADAPTATION_TO_HYPOXIA_DN 0.026259936

LI_INDUCED_T_TO_NATURAL_KILLER_DN 0.026398975

SHAFFER_IRF4_TARGETS_IN_ACTIVATED_B_LYMPHOCYTE 0.027347382

LU_AGING_BRAIN_UP 0.027616156

REACTOME_INTERFERON_GAMMA_SIGNALING 0.02788979

DELPUECH_FOXO3_TARGETS_DN 0.027817665

BIOCARTA_NKT_PATHWAY 0.027654722

PARK_TRETINOIN_RESPONSE_AND_PML_RARA_FUSION 0.02805681

BOSCO_TH1_CYTOTOXIC_MODULE 0.027849048

GUILLAUMOND_KLF10_TARGETS_UP 0.030350104

BOYAULT_LIVER_CANCER_SUBCLASS_G5_DN 0.030912133

TARTE_PLASMA_CELL_VS_B_LYMPHOCYTE_DN 0.030593451

COLIN_PILOCYTIC_ASTROCYTOMA_VS_GLIOBLASTOMA_DN 0.03238081

HUANG_GATA2_TARGETS_UP 0.032215368

BURTON_ADIPOGENESIS_PEAK_AT_0HR 0.03686059

NAKAMURA_METASTASIS_MODEL_UP 0.0365904

SARTIPY_BLUNTED_BY_INSULIN_RESISTANCE_DN 0.036242183

MOSERLE_IFNA_RESPONSE 0.036313888

VERHAAK_GLIOBLASTOMA_MESENCHYMAL 0.036271892

KEGG_CHEMOKINE_SIGNALING_PATHWAY 0.036311574

HESS_TARGETS_OF_HOXA9_AND_MEIS1_DN 0.036923986

BRACHAT_RESPONSE_TO_METHOTREXATE_UP 0.037974447

WANG_RESPONSE_TO_GSK3_INHIBITOR_SB216763_UP 0.04008004

COULOUARN_TEMPORAL_TGFB1_SIGNATURE_UP 0.0408265

REACTOME_BASIGIN_INTERACTIONS 0.040668692

NAKAMURA_METASTASIS 0.04385387

SMIRNOV_RESPONSE_TO_IR_2HR_DN 0.043775413

YAMAZAKI_TCEB3_TARGETS_UP 0.043831937

YAO_TEMPORAL_RESPONSE_TO_PROGESTERONE_CLUSTER_1 0.043718435

ZHENG_FOXP3_TARGETS_IN_T_LYMPHOCYTE_DN 0.043347456

PLASARI_NFIC_TARGETS_BASAL_DN 0.04523399

PID_GLYPICAN_1PATHWAY 0.04625897

JOHANSSON_BRAIN_CANCER_EARLY_VS_LATE_DN 0.046146955

MOOTHA_GLYCOGEN_METABOLISM 0.04705981

VECCHI_GASTRIC_CANCER_ADVANCED_VS_EARLY_UP 0.04669417

CERVERA_SDHB_TARGETS_1_DN 0.048324384

KIM_GLIS2_TARGETS_UP 0.04961473

HELLER_SILENCED_BY_METHYLATION_DN 0.04931493

Supplementary Table S12. Enrichment for transcription factor binding sites in down-regulated genes in BCR-ABL1+ pre-B cells.

Term Overlap P-value Adjusted P-value

MYC_MEL cell line_mm9 287/2000 0 0

POLR2AphosphoS5_MEL cell line_mm9 333/2661 0 0

POLR2A_MEL cell line_mm9 491/4890 0 0

BHLHE40_MEL cell line_mm9 254/2000 0 0

CHD1_CH12.LX_mm9 232/2000 1.48E-28 1.0066E-26

POLR2A_ES-Bruce4_mm9 238/2000 1E-30 1.11E-28

UBTF_CH12.LX_mm9 233/2000 6.3E-29 4.669E-27

UBTF_MEL cell line_mm9 236/2000 5E-30 4.8E-28

MAX_C2C12_mm9 233/2000 6.3E-29 4.669E-27

MYOG_myocyte_mm9 349/3623 3E-29 2.683E-27

MAX_MEL cell line_mm9 226/2000 2.2702E-26 1.23498E-24

USF2_MEL cell line_mm9 233/2106 4.6267E-26 2.35962E-24

CTCF_MEL cell line_mm9 425/4882 1.366E-27 8.5764E-26

POLR2AphosphoS5_G1E_mm9 262/2517 8.3261E-26 3.99653E-24

USF1_myocyte_mm9 220/2000 2.93354E-24 1.25988E-22

RCOR1_CH12.LX_mm9 219/2000 6.48529E-24 2.52E-22

USF1_C2C12_mm9 215/2000 1.47498E-22 5.23297E-21

POLR2A_bone marrow macrophage_mm9 218/2000 1.42675E-23 5.29193E-22

GATA1_G1E-ER4_mm9 352/3942 6.35379E-24 2.52E-22

EP300_ES-Bruce4_mm9 212/2000 1.45826E-21 4.10323E-20

Supplementary Table S13. Enrichment for transcription factor binding sites in down-regulated genes in WT pre-B cells.

Term Overlap P-value Adjusted P-value

MYC_MEL cell line_mm9 74/2000 3.1485E-26 2.55344E-23

MAX_MEL cell line_mm9 55/2000 8.32131E-14 2.24953E-11

MAX_C2C12_mm9 55/2000 8.32131E-14 2.24953E-11

MXI1_MEL cell line_mm9 53/2000 1.07916E-12 2.188E-10

SIN3A_MEL cell line_mm9 51/2000 1.27542E-11 1.47766E-09

GATA1_MEL cell line_mm9 65/2994 1.02341E-11 1.47766E-09

USF2_CH12.LX_mm9 49/2000 1.37035E-10 1.11135E-08

POLR2A_MEL cell line_mm9 87/4890 3.6134E-11 3.66309E-09

MYC_CH12.LX_mm9 47/2000 1.33502E-09 8.32844E-08

MAX_myocyte_mm9 33/1160 7.07243E-09 4.09696E-07

RCOR1_CH12.LX_mm9 45/2000 1.17594E-08 5.96057E-07

CTCF_CH12.LX_mm9 67/3777 2.05794E-08 9.81759E-07

USF1_myocyte_mm9 43/2000 9.33694E-08 3.0289E-06

USF2_MEL cell line_mm9 45/2106 5.26156E-08 2.03196E-06

BHLHE40_MEL cell line_mm9 43/2000 9.33694E-08 3.0289E-06

E2F4_myocyte_mm9 44/2000 3.35752E-08 1.3758E-06

HCFC1_CH12.LX_mm9 44/2000 3.35752E-08 1.3758E-06

CTCF_G1E_mm9 46/2246 1.2328E-07 3.84539E-06

Supplementary Table S14. Enrichment for transcription factor binding sites in up-regulated genes in BCR-ABL1+ pre-B cells.

Term Overlap P-value Adjusted P-value

EP300_CH12.LX_mm9 111/2000 9.66518E-24 7.88679E-21

ETS1_CH12.LX_mm9 91/2000 2.94304E-14 7.03541E-12

ETS1_MEL cell line_mm9 88/1902 3.44873E-14 7.03541E-12

CHD1_CH12.LX_mm9 91/2000 2.94304E-14 7.03541E-12

ZMIZ1_MEL cell line_mm9 70/1392 5.55736E-13 9.06962E-11

JUND_CH12.LX_mm9 68/1454 2.75735E-11 3.74999E-09

POLR2AphosphoS5_G1E-ER4_mm9 81/1944 6.88767E-11 8.02906E-09

TCF12_myocyte_mm9 58/1223 5.64962E-10 4.37007E-08

POLR2AphosphoS2_MEL cell line_mm9 82/2000 1.09738E-10 1.11933E-08

CHD2_MEL cell line_mm9 77/1826 1.2968E-10 1.17577E-08

ZKSCAN1_CH12.LX_mm9 58/1240 9.23561E-10 6.28021E-08

POLR2A_bone marrow macrophage_mm9 80/2000 5.89102E-10 4.37007E-08

TCF3_myocyte_mm9 77/1987 5.02601E-09 2.56327E-07

GATA1_erythroblast_mm9 76/1971 7.89927E-09 3.79165E-07

CTCF_MEL cell line_mm9 149/4882 1.81246E-09 1.13767E-07

MYOD1_myocyte_mm9 107/3164 4.85621E-09 2.56327E-07

RCOR1_CH12.LX_mm9 75/2000 3.07702E-08 1.14129E-06

JUN_CH12.LX_mm9 65/1659 6.32639E-08 2.12184E-06

ZC3H11A_CH12.LX_mm9 59/1429 4.96114E-08 1.76013E-06

POLR2A_cerebellum_mm9 75/2000 3.07702E-08 1.14129E-06

TBP_MEL cell line_mm9 75/2000 3.07702E-08 1.14129E-06

POLR2A_CH12.LX_mm9 75/2000 3.07702E-08 1.14129E-06

POLR2A_liver_mm9 75/2000 3.07702E-08 1.14129E-06

POLR2A_MEL cell line_mm9 148/4890 3.71639E-09 2.16613E-07

SMC3_MEL cell line_mm9 73/2000 1.35332E-07 3.94395E-06

Supplementary Table S15. Enrichment for transcription factor binding sites in up-regulated genes in WT pre-B cells.

Term Overlap P-value Adjusted P-value

EP300_CH12.LX_mm9 106/2000 6.49018E-21 5.29598E-18

ETS1_MEL cell line_mm9 94/1902 1.24803E-16 5.09196E-14

MYOD1_myocyte_mm9 121/3164 2.18676E-13 5.948E-11

CHD1_CH12.LX_mm9 82/2000 1.62189E-10 2.64692E-08

JUND_CH12.LX_mm9 63/1454 3.91351E-09 3.16295E-07

ZMIZ1_MEL cell line_mm9 63/1392 7.75352E-10 9.03839E-08

RAD21_CH12.LX_mm9 78/2000 4.26378E-09 3.16295E-07

MYOG_myocyte_mm9 123/3623 2.95062E-10 4.01284E-08

ETS1_CH12.LX_mm9 77/2000 9.32257E-09 5.07148E-07

TCF3_myocyte_mm9 77/1987 7.11382E-09 4.46529E-07

CTCF_MEL cell line_mm9 150/4882 1.76046E-09 1.79567E-07

MAZ_MEL cell line_mm9 78/2000 4.26378E-09 3.16295E-07

BHLHE40_MEL cell line_mm9 76/2000 2.00946E-08 1.02482E-06

POLR2A_bone marrow macrophage_mm9 77/2000 9.32257E-09 5.07148E-07

JUN_CH12.LX_mm9 65/1659 8.46638E-08 3.45428E-06

TAL1_MEL cell line_mm9 83/2290 3.07716E-08 1.47704E-06

EP300_MEL cell line_mm9 74/2000 8.93982E-08 3.47376E-06

CHD1_MEL cell line_mm9 36/691 1.7944E-07 6.65561E-06

CTCF_kidney_mm9 75/2000 4.26937E-08 1.93545E-06

POLR2A_MEL cell line_mm9 148/4890 6.54133E-09 4.4481E-07

TCF12_myocyte_mm9 51/1223 4.11268E-07 1.34238E-05

GATA1_G1E-ER4_mm9 122/3942 7.36701E-08 3.16394E-06

GATA1_erythroblast_mm9 72/1971 2.20021E-07 7.80595E-06

MAFK_CH12.LX_mm9 71/2000 7.51059E-07 2.35717E-05