NOTCH2 blockade alters the expression of diverse genes
| Gene . | Pathway/Function . | log2 fold change . | Fold change . | P . | Adjusted P . |
|---|---|---|---|---|---|
| DNASE1L3 | Apoptosis/DNA hydrolysis | −2.50 | −5.65 | 7.04 × 10−20 | 9.07 × 10−16 |
| HES4 | [NOTCH pathway] | −2.97 | −7.86 | 2.79 × 10−17 | 1.80 × 10−13 |
| CR2 | BCR/Complement binding | −1.76 | −3.38 | 2.70 × 10−16 | 1.16 × 10−12 |
| FOS* | Cell-cycle control/Transcription factor, MAPK pathway | 1.55 | 2.93 | 1.37 × 10−9 | 4.42 × 10−6 |
| CD300A | Immune response/Inhibitory receptor for phosphatidylserine | −1.80 | −3.49 | 2.00 × 10−8 | 3.70 × 10−5 |
| DTL | Cell-cycle control, DNA damage response/E3 ubiquitin ligase activity | −1.46 | −2.74 | 1.45 × 10−8 | 3.70 × 10−5 |
| FCRL4 | B-cell receptor/Signal modulation/Marginal zone B cells | −1.59 | −3.01 | 2.01 × 10−8 | 3.70 × 10−5 |
| MMP9* | Extracellular matrix organization/[NOTCH regulation reported] | 1.77 | 3.40 | 2.90 × 10−8 | 4.66 × 10−5 |
| IL12RB2 | Immune response | −1.59 | −3.01 | 1.91 × 10−7 | 2.53 × 10−4 |
| MACROD2* | Signal modulation/Wnt pathway | 0.951 | 1.93 | 1.96 × 10−7 | 2.53 × 10−4 |
| ABHD6 | Signal modulation/GPCR signaling | −1.15 | −2.21 | 5.56 × 10−7 | 6.51 × 10−4 |
| CDC6 | Cell-cycle control | −1.34 | −2.52 | 6.26 × 10−7 | 6.72 × 10−4 |
| CHI3L2 | Cartilage biogenesis | −1.49 | −2.82 | 9.30 × 10−7 | 9.21 × 10−4 |
| DUSP1* | Signal modulation/MAPK pathway/[NOTCH regulation reported] | 1.21 | 2.31 | 1.61 × 10−6 | 1.49 × 10−3 |
| C11orf21* | (Unknown) | 1.53 | 2.89 | 2.52 × 10−6 | 2.15 × 10−3 |
| TFRC | Immune response/Iron metabolism | −1.04 | −2.05 | 2.67 × 10−6 | 2.15 × 10−3 |
| RHOBTB1 | GTPase activity/GPCR signaling | −1.13 | −2.19 | 6.94 × 10−6 | 5.26 × 10−3 |
| CD68* | Scavenger receptor | 0.998 | 2.00 | 7.40 × 10−6 | 5.29 × 10−3 |
| SLC19A1 | Folate transport/Cell-cycle control | −1.09 | −2.14 | 8.60 × 10−6 | 5.83 × 10−3 |
| CD14* | Immune response/LPS binding | 1.51 | 2.84 | 1.14 × 10−5 | 6.39 × 10−3 |
| DDN | Apoptosis | −1.50 | −2.83 | 1.07 × 10−5 | 6.39 × 10−3 |
| MRC1* | Immune response/Mannose binding | 1.56 | 2.95 | 1.12 × 10−5 | 6.39 × 10−3 |
| RSAD2* | Immune response/Antiviral response | 1.33 | 2.51 | 1.02 × 10−5 | 6.39 × 10−3 |
| IFIT1* | Immune response/Antiviral response/RNA binding | 1.11 | 2.17 | 1.46 × 10−5 | 7.85 × 10−3 |
| HMOX1* | Heme catabolism/NF-κB signaling | 1.03 | 2.04 | 1.94 × 10−5 | .010 |
| SNX29P2* | (Unknown; pseudogene) | 0.937 | 1.91 | 2.20 × 10−5 | .011 |
| PSTPIP1* | BCR/Immune response/Actin cytoskeleton | 0.889 | 1.85 | 2.39 × 10−5 | .011 |
| MACROD1 | Signal modulation/Deacetylation of ADP ribose moieties | −1.01 | −2.01 | 2.60 × 10−5 | .012 |
| PPIF | Apoptosis/Protein folding | −0.896 | −1.86 | 2.81 × 10−5 | .012 |
| NCF2* | Immune response/GPCR signaling | 0.762 | 1.70 | 6.52 × 10−5 | .027 |
| TNFSF12* | Immune response/Apoptosis/[NOTCH regulation reported] | 0.886 | 1.85 | 6.56 × 10−5 | .027 |
| BIRC5 | Apoptosis/Cell-cycle control/[NOTCH regulation reported] | −1.39 | −2.61 | 7.24 × 10−5 | .027 |
| CTPS1 | Immune response/Nucleic acid biosynthesis, metabolism | −0.946 | −1.93 | 7.04 × 10−5 | .027 |
| FKBP4 | Immune response/Protein folding, trafficking/[Negative regulator of IRF4] | −0.862 | −1.82 | 6.84 × 10−5 | .027 |
| SLC16A9 | Metabolism/Membrane transport | −1.35 | −2.55 | 8.87 × 10−5 | .033 |
| CARNS1* | Metabolism/Amino acid biosynthesis | 1.25 | 2.37 | 9.51 × 10−5 | .033 |
| CDC25A | BCR/Cell-cycle control, DNA damage response/MAPK pathway | −1.24 | −2.36 | 9.48 × 10−5 | .033 |
| CYP2J2 | Metabolism/Arachidonic acid metabolism | −1.37 | −2.58 | 9.90 × 10−5 | .034 |
| ANPEP* | Metabolism/Golgi protein transport | 1.36 | 2.57 | 1.19 × 10−4 | .035 |
| C5AR1* | Immune response/Complement binding | 1.34 | 2.53 | 1.22 × 10−4 | .035 |
| CTSL1* | Immune response/Antigen processing and presentation | 1.36 | 2.56 | 1.20 × 10−4 | .035 |
| HNRNPAB | mRNA splicing | −0.750 | −1.68 | 1.19 × 10−4 | .035 |
| LCN10 | Carrier protein activity | −0.859 | −1.81 | 1.18 × 10−4 | .035 |
| MOV10* | Immune response/RNA helicase activity, mRNA processing | 0.942 | 1.92 | 1.17 × 10−4 | .035 |
| PTRF* | Transcriptional regulation | 1.27 | 2.41 | 1.13 × 10−4 | .035 |
| ANKLE1 | Endonuclease activity | −0.864 | −1.82 | 1.35 × 10−4 | .037 |
| FCGBP* | Maintenance of mucosal integrity | 1.35 | 2.55 | 1.37 × 10−4 | .037 |
| CORO2B* | Cytoskeletal reorganization | 1.33 | 2.52 | 1.47 × 10−4 | .039 |
| IL8* | Immune response/Chemoattraction | 1.29 | 2.45 | 1.49 × 10−4 | .039 |
| MYBL2 | Cell-cycle control | −1.01 | −2.02 | 1.52 × 10−4 | .039 |
| IL6R | Immune response/Plasma cell development/[NOTCH regulation reported] | −0.713 | −1.64 | 1.61 × 10−4 | .041 |
| DAB2* | Immune response/Signal modulation/Endocytosis/Wnt pathway | 1.27 | 2.42 | 1.78 × 10−4 | .043 |
| LRRC37A4P* | (Unknown; pseudogene) | 1.33 | 2.51 | 1.83 × 10−4 | .043 |
| SLC16A1 | Metabolism/Membrane transport | −0.991 | −1.99 | 1.72 × 10−4 | .043 |
| SRM | Metabolism/Spermidine biosynthesis/Amino acid metabolism | −0.709 | −1.63 | 1.85 × 10−4 | .043 |
| TTLL12 | Cell-cycle control/Cytoskeletal reorganization | −0.746 | −1.68 | 1.82 × 10−4 | .043 |
| SKA3 | Cell-cycle control/Cytoskeletal reorganization | −1.26 | −2.39 | 2.02 × 10−4 | .045 |
| TOMM40 | Metabolism/Mitochondrial membrane transport | −0.680 | −1.60 | 2.02 × 10−4 | .045 |
| MEST | Wnt pathway/Genetic imprinting | −0.998 | −2.00 | 2.10 × 10−4 | .046 |
| ORC6 | Cell-cycle control | −1.07 | −2.10 | 2.25 × 10−4 | .047 |
| RGS16 | Immune response/GPCR signaling | −0.934 | −1.91 | 2.21 × 10−4 | .047 |
| PAICS | Metabolism/Purine metabolism | −0.715 | −1.64 | 2.38 × 10−4 | .049 |
| UBE2C | Cell-cycle control/E2 ubiquitin ligase activity | −1.30 | −2.46 | 2.36 × 10−4 | .049 |
| LOC100506123* | (Unknown; ncRNA class gene) | 1.28 | 2.42 | 2.48 × 10−4 | .049 |
| TYMS | Metabolism/Pyrimidine metabolism | −0.999 | −2.00 | 2.47 × 10−4 | .049 |
| Gene . | Pathway/Function . | log2 fold change . | Fold change . | P . | Adjusted P . |
|---|---|---|---|---|---|
| DNASE1L3 | Apoptosis/DNA hydrolysis | −2.50 | −5.65 | 7.04 × 10−20 | 9.07 × 10−16 |
| HES4 | [NOTCH pathway] | −2.97 | −7.86 | 2.79 × 10−17 | 1.80 × 10−13 |
| CR2 | BCR/Complement binding | −1.76 | −3.38 | 2.70 × 10−16 | 1.16 × 10−12 |
| FOS* | Cell-cycle control/Transcription factor, MAPK pathway | 1.55 | 2.93 | 1.37 × 10−9 | 4.42 × 10−6 |
| CD300A | Immune response/Inhibitory receptor for phosphatidylserine | −1.80 | −3.49 | 2.00 × 10−8 | 3.70 × 10−5 |
| DTL | Cell-cycle control, DNA damage response/E3 ubiquitin ligase activity | −1.46 | −2.74 | 1.45 × 10−8 | 3.70 × 10−5 |
| FCRL4 | B-cell receptor/Signal modulation/Marginal zone B cells | −1.59 | −3.01 | 2.01 × 10−8 | 3.70 × 10−5 |
| MMP9* | Extracellular matrix organization/[NOTCH regulation reported] | 1.77 | 3.40 | 2.90 × 10−8 | 4.66 × 10−5 |
| IL12RB2 | Immune response | −1.59 | −3.01 | 1.91 × 10−7 | 2.53 × 10−4 |
| MACROD2* | Signal modulation/Wnt pathway | 0.951 | 1.93 | 1.96 × 10−7 | 2.53 × 10−4 |
| ABHD6 | Signal modulation/GPCR signaling | −1.15 | −2.21 | 5.56 × 10−7 | 6.51 × 10−4 |
| CDC6 | Cell-cycle control | −1.34 | −2.52 | 6.26 × 10−7 | 6.72 × 10−4 |
| CHI3L2 | Cartilage biogenesis | −1.49 | −2.82 | 9.30 × 10−7 | 9.21 × 10−4 |
| DUSP1* | Signal modulation/MAPK pathway/[NOTCH regulation reported] | 1.21 | 2.31 | 1.61 × 10−6 | 1.49 × 10−3 |
| C11orf21* | (Unknown) | 1.53 | 2.89 | 2.52 × 10−6 | 2.15 × 10−3 |
| TFRC | Immune response/Iron metabolism | −1.04 | −2.05 | 2.67 × 10−6 | 2.15 × 10−3 |
| RHOBTB1 | GTPase activity/GPCR signaling | −1.13 | −2.19 | 6.94 × 10−6 | 5.26 × 10−3 |
| CD68* | Scavenger receptor | 0.998 | 2.00 | 7.40 × 10−6 | 5.29 × 10−3 |
| SLC19A1 | Folate transport/Cell-cycle control | −1.09 | −2.14 | 8.60 × 10−6 | 5.83 × 10−3 |
| CD14* | Immune response/LPS binding | 1.51 | 2.84 | 1.14 × 10−5 | 6.39 × 10−3 |
| DDN | Apoptosis | −1.50 | −2.83 | 1.07 × 10−5 | 6.39 × 10−3 |
| MRC1* | Immune response/Mannose binding | 1.56 | 2.95 | 1.12 × 10−5 | 6.39 × 10−3 |
| RSAD2* | Immune response/Antiviral response | 1.33 | 2.51 | 1.02 × 10−5 | 6.39 × 10−3 |
| IFIT1* | Immune response/Antiviral response/RNA binding | 1.11 | 2.17 | 1.46 × 10−5 | 7.85 × 10−3 |
| HMOX1* | Heme catabolism/NF-κB signaling | 1.03 | 2.04 | 1.94 × 10−5 | .010 |
| SNX29P2* | (Unknown; pseudogene) | 0.937 | 1.91 | 2.20 × 10−5 | .011 |
| PSTPIP1* | BCR/Immune response/Actin cytoskeleton | 0.889 | 1.85 | 2.39 × 10−5 | .011 |
| MACROD1 | Signal modulation/Deacetylation of ADP ribose moieties | −1.01 | −2.01 | 2.60 × 10−5 | .012 |
| PPIF | Apoptosis/Protein folding | −0.896 | −1.86 | 2.81 × 10−5 | .012 |
| NCF2* | Immune response/GPCR signaling | 0.762 | 1.70 | 6.52 × 10−5 | .027 |
| TNFSF12* | Immune response/Apoptosis/[NOTCH regulation reported] | 0.886 | 1.85 | 6.56 × 10−5 | .027 |
| BIRC5 | Apoptosis/Cell-cycle control/[NOTCH regulation reported] | −1.39 | −2.61 | 7.24 × 10−5 | .027 |
| CTPS1 | Immune response/Nucleic acid biosynthesis, metabolism | −0.946 | −1.93 | 7.04 × 10−5 | .027 |
| FKBP4 | Immune response/Protein folding, trafficking/[Negative regulator of IRF4] | −0.862 | −1.82 | 6.84 × 10−5 | .027 |
| SLC16A9 | Metabolism/Membrane transport | −1.35 | −2.55 | 8.87 × 10−5 | .033 |
| CARNS1* | Metabolism/Amino acid biosynthesis | 1.25 | 2.37 | 9.51 × 10−5 | .033 |
| CDC25A | BCR/Cell-cycle control, DNA damage response/MAPK pathway | −1.24 | −2.36 | 9.48 × 10−5 | .033 |
| CYP2J2 | Metabolism/Arachidonic acid metabolism | −1.37 | −2.58 | 9.90 × 10−5 | .034 |
| ANPEP* | Metabolism/Golgi protein transport | 1.36 | 2.57 | 1.19 × 10−4 | .035 |
| C5AR1* | Immune response/Complement binding | 1.34 | 2.53 | 1.22 × 10−4 | .035 |
| CTSL1* | Immune response/Antigen processing and presentation | 1.36 | 2.56 | 1.20 × 10−4 | .035 |
| HNRNPAB | mRNA splicing | −0.750 | −1.68 | 1.19 × 10−4 | .035 |
| LCN10 | Carrier protein activity | −0.859 | −1.81 | 1.18 × 10−4 | .035 |
| MOV10* | Immune response/RNA helicase activity, mRNA processing | 0.942 | 1.92 | 1.17 × 10−4 | .035 |
| PTRF* | Transcriptional regulation | 1.27 | 2.41 | 1.13 × 10−4 | .035 |
| ANKLE1 | Endonuclease activity | −0.864 | −1.82 | 1.35 × 10−4 | .037 |
| FCGBP* | Maintenance of mucosal integrity | 1.35 | 2.55 | 1.37 × 10−4 | .037 |
| CORO2B* | Cytoskeletal reorganization | 1.33 | 2.52 | 1.47 × 10−4 | .039 |
| IL8* | Immune response/Chemoattraction | 1.29 | 2.45 | 1.49 × 10−4 | .039 |
| MYBL2 | Cell-cycle control | −1.01 | −2.02 | 1.52 × 10−4 | .039 |
| IL6R | Immune response/Plasma cell development/[NOTCH regulation reported] | −0.713 | −1.64 | 1.61 × 10−4 | .041 |
| DAB2* | Immune response/Signal modulation/Endocytosis/Wnt pathway | 1.27 | 2.42 | 1.78 × 10−4 | .043 |
| LRRC37A4P* | (Unknown; pseudogene) | 1.33 | 2.51 | 1.83 × 10−4 | .043 |
| SLC16A1 | Metabolism/Membrane transport | −0.991 | −1.99 | 1.72 × 10−4 | .043 |
| SRM | Metabolism/Spermidine biosynthesis/Amino acid metabolism | −0.709 | −1.63 | 1.85 × 10−4 | .043 |
| TTLL12 | Cell-cycle control/Cytoskeletal reorganization | −0.746 | −1.68 | 1.82 × 10−4 | .043 |
| SKA3 | Cell-cycle control/Cytoskeletal reorganization | −1.26 | −2.39 | 2.02 × 10−4 | .045 |
| TOMM40 | Metabolism/Mitochondrial membrane transport | −0.680 | −1.60 | 2.02 × 10−4 | .045 |
| MEST | Wnt pathway/Genetic imprinting | −0.998 | −2.00 | 2.10 × 10−4 | .046 |
| ORC6 | Cell-cycle control | −1.07 | −2.10 | 2.25 × 10−4 | .047 |
| RGS16 | Immune response/GPCR signaling | −0.934 | −1.91 | 2.21 × 10−4 | .047 |
| PAICS | Metabolism/Purine metabolism | −0.715 | −1.64 | 2.38 × 10−4 | .049 |
| UBE2C | Cell-cycle control/E2 ubiquitin ligase activity | −1.30 | −2.46 | 2.36 × 10−4 | .049 |
| LOC100506123* | (Unknown; ncRNA class gene) | 1.28 | 2.42 | 2.48 × 10−4 | .049 |
| TYMS | Metabolism/Pyrimidine metabolism | −0.999 | −2.00 | 2.47 × 10−4 | .049 |
NOTCH2 blockade alters the expression of diverse genes in NOTCH2/BCR-stimulated B cells from active cGVHD patients. RNA samples used in the NanoString analysis described in Figure 2C were also subjected to Illumina HiSeq 125-bp paired-end sequencing. Genes shown represent those significantly altered by NOTCH2 blockade ranked in order of significance based on the adjusted P value, determined as described in supplemental Methods. All genes with an adjusted P value of <.05 are shown.
GPCR, G-protein–coupled receptor; LPS, lipopolysaccharide; mRNA, messenger RNA; ncRNA, noncoding RNA.
Genes shown in bold are downregulated by NOTCH2 blockade.
Genes upregulated by NOTCH2 blockade.