Table 5.

Genes with significantly lower average gene expression in AL plasma cells than in MM cells


Gene symbol

Name of gene

Genes the focus gene regulates

Genes by which the focus gene is regulated

Genes the focus genes binds

Value of the test statistic
MYC*  v-myc myelocytomatosis viral oncogene homolog  CSK2, CDKN1A, NFκB, CDC25A, PDGFRB RGFB1, IL3, CDKN1B, EPO, KRAS2, RELA TRADD; RBL1; E2F1, 2, 3, 4, and 5  –3.78  
p53*  Tumor protein p53  JUN, CDKN1A, IGFBP3, NFκB1, RELA, CREBBP IL3, ATM, ETS1, NFκB, MAPK8 MDM2, CREB, CDKN2A, CREBBP  –3.54  
E2A*  E2A Ig enhancer binding factor (E12/E47)  CDKN1a, PAX-5, RAG1, VPREB1, CD79A EBP, PAX3, IL6, PIP, NOTCH1 HOXB7, HOXB8, HOXA5, MYOG, MYOD1, RB1, EBF  –4.17  
XRCC4  X-ray repair factor 4  POLM, LIG4 POLM, KITLG LIG4, XRCC5, PRKDC, DNA Ligase  –3.43  
XRCC5*  Ku 80  Osteocalcin, DNA-PK, RNA Pol II LOX, CXCL12, p53, DNA-PK XRCC4, PCNA, Telomerase  –3.99  
TXN  Thioredoxin  VEGF, CD4, PTEN, IL2, NFκB, BCL2, TRAF6 ILlb, MYC, ATM CREB3, PTEN, NFκB  –5.88  
IL6ST*  IL6 signal transducer  IL6, JUNB, JAK1, 2, STAT1, 3, 5B TNF, IL6, OSM, IL6R, SOCS STAT3; SOCS3; IL11; IL6; JAK1, 2; STAT1  –3.71  
TGFB1  Transforming growth factor B1  CDK2, CDKN1A, Cyclin D, CDK6, CDKN1B, MYC IL4, IL13, TNF TGFBR, EGR1, ITGAV, A2M  –3.21  
CASP3*  Caspase 3  CASP8, 9, BID, CASP6, SSB AKT1, BID, TNF CASP1, CDKN1A, BCL2L1, STAT1, CCND3  –3.00  
RELA  NFκB p65 subunit  JUNB, CD86, CD44, TNFRSF5, CCR7, ICAM, BCL2L1, TNFRSF6 PPARγ, TNF, FADD, TRADD, TNFRSF1A, p53, IKBKB MMP9, NFKB1A, IFNG, IL6, IL4, IL12B  –3.91  
CD47  CD47 antigen  THBS1, PTPN2 ERBB2, HOXa11, CSCL12 UBQLN1, SRC, LICAM  –4.33  
CDK4*  Cyclin-dependent kinase 4  RBL1; CDK2; MYC; RB1; CDKN1B, C; DKN1A; CDK6 IL4, MYC, CDKN1A, CDKN1B, BCL2, PPAR6, BCL2L1 PCNA, MDM2, p53, CCND1, CDKN1C, CDKN1A, CDKN1B, CDK6, CCND2  –4.69  
CDK5  Cyclin-dependent kinase 5  MYC, JUN, MAPK10, APP CDK5R1, Laminin 1, PHO80 CCND1, SET, ACTN1, PHO80  –3.61  
CDK9  Cyclin-dependent kinase 9  MYC, RB1, MBP, MYOD1 Alkaline phosphatase, PTEN, IL6, TAT TAT, RB1, MYC, RELA, Hsp90, MYOD1, NFκB1  –4.42  
CDC37  Cell division cycle 37 homolog  CDK4, Hsp90 CDKN2A, LCK, CCL5 CCND1, CDK6, Hsp90, TRAF3, SRC, IKBKG  –3.63  
CCNB1  Cyclin B1  RB1, CDC25A, CDKN1B, p53, GRO TGFB1, CDC25A, CDKN1A, MYC, PTEN, p53 CDC2, CDC25A, CDKN1A, RELA, PAP, MYC, ERBB2  –4.06  
PSEN1  Presenilin 1  LRP1, APP, Gamma secretase, JUN, CCND1, NOTCH1 ETS1, p53, PSEN2, CASP3, IL1B, GSK3B APBA1, APBA2, NOTCH1, APP, Alpha catenin, NOTCH2 and 3  –3.82  
PSEN2  Presenilin 2  APP, NOTCH1, ERBB4, BAX, PSEN1, p53, BCL2, CASP3 PSEN1, p53, CASP3, Ubiquilin, NCSTN NOTCH1, APP, PEN2, PSEN1, Gamma secretase, PSEN2, BCL2L1  –3.36  
UCHL1  Ubiquitin carboxyl-terminal esterase L1  Ubiquitin HNF4a, MYCN Ubiquitin, CDKN1B, SNCA  –3.12  
PTEN
 
Phosphatase and tensin homolog
 
BCL2, CASP3, TNFRSF6, AKT1, CSN2
 
ERBB2, BCL2, TGFB1, HBX, EGR1
 
MAGI-3, AIP1, TXN, p53
 
–3.90
 

Gene symbol

Name of gene

Genes the focus gene regulates

Genes by which the focus gene is regulated

Genes the focus genes binds

Value of the test statistic
MYC*  v-myc myelocytomatosis viral oncogene homolog  CSK2, CDKN1A, NFκB, CDC25A, PDGFRB RGFB1, IL3, CDKN1B, EPO, KRAS2, RELA TRADD; RBL1; E2F1, 2, 3, 4, and 5  –3.78  
p53*  Tumor protein p53  JUN, CDKN1A, IGFBP3, NFκB1, RELA, CREBBP IL3, ATM, ETS1, NFκB, MAPK8 MDM2, CREB, CDKN2A, CREBBP  –3.54  
E2A*  E2A Ig enhancer binding factor (E12/E47)  CDKN1a, PAX-5, RAG1, VPREB1, CD79A EBP, PAX3, IL6, PIP, NOTCH1 HOXB7, HOXB8, HOXA5, MYOG, MYOD1, RB1, EBF  –4.17  
XRCC4  X-ray repair factor 4  POLM, LIG4 POLM, KITLG LIG4, XRCC5, PRKDC, DNA Ligase  –3.43  
XRCC5*  Ku 80  Osteocalcin, DNA-PK, RNA Pol II LOX, CXCL12, p53, DNA-PK XRCC4, PCNA, Telomerase  –3.99  
TXN  Thioredoxin  VEGF, CD4, PTEN, IL2, NFκB, BCL2, TRAF6 ILlb, MYC, ATM CREB3, PTEN, NFκB  –5.88  
IL6ST*  IL6 signal transducer  IL6, JUNB, JAK1, 2, STAT1, 3, 5B TNF, IL6, OSM, IL6R, SOCS STAT3; SOCS3; IL11; IL6; JAK1, 2; STAT1  –3.71  
TGFB1  Transforming growth factor B1  CDK2, CDKN1A, Cyclin D, CDK6, CDKN1B, MYC IL4, IL13, TNF TGFBR, EGR1, ITGAV, A2M  –3.21  
CASP3*  Caspase 3  CASP8, 9, BID, CASP6, SSB AKT1, BID, TNF CASP1, CDKN1A, BCL2L1, STAT1, CCND3  –3.00  
RELA  NFκB p65 subunit  JUNB, CD86, CD44, TNFRSF5, CCR7, ICAM, BCL2L1, TNFRSF6 PPARγ, TNF, FADD, TRADD, TNFRSF1A, p53, IKBKB MMP9, NFKB1A, IFNG, IL6, IL4, IL12B  –3.91  
CD47  CD47 antigen  THBS1, PTPN2 ERBB2, HOXa11, CSCL12 UBQLN1, SRC, LICAM  –4.33  
CDK4*  Cyclin-dependent kinase 4  RBL1; CDK2; MYC; RB1; CDKN1B, C; DKN1A; CDK6 IL4, MYC, CDKN1A, CDKN1B, BCL2, PPAR6, BCL2L1 PCNA, MDM2, p53, CCND1, CDKN1C, CDKN1A, CDKN1B, CDK6, CCND2  –4.69  
CDK5  Cyclin-dependent kinase 5  MYC, JUN, MAPK10, APP CDK5R1, Laminin 1, PHO80 CCND1, SET, ACTN1, PHO80  –3.61  
CDK9  Cyclin-dependent kinase 9  MYC, RB1, MBP, MYOD1 Alkaline phosphatase, PTEN, IL6, TAT TAT, RB1, MYC, RELA, Hsp90, MYOD1, NFκB1  –4.42  
CDC37  Cell division cycle 37 homolog  CDK4, Hsp90 CDKN2A, LCK, CCL5 CCND1, CDK6, Hsp90, TRAF3, SRC, IKBKG  –3.63  
CCNB1  Cyclin B1  RB1, CDC25A, CDKN1B, p53, GRO TGFB1, CDC25A, CDKN1A, MYC, PTEN, p53 CDC2, CDC25A, CDKN1A, RELA, PAP, MYC, ERBB2  –4.06  
PSEN1  Presenilin 1  LRP1, APP, Gamma secretase, JUN, CCND1, NOTCH1 ETS1, p53, PSEN2, CASP3, IL1B, GSK3B APBA1, APBA2, NOTCH1, APP, Alpha catenin, NOTCH2 and 3  –3.82  
PSEN2  Presenilin 2  APP, NOTCH1, ERBB4, BAX, PSEN1, p53, BCL2, CASP3 PSEN1, p53, CASP3, Ubiquilin, NCSTN NOTCH1, APP, PEN2, PSEN1, Gamma secretase, PSEN2, BCL2L1  –3.36  
UCHL1  Ubiquitin carboxyl-terminal esterase L1  Ubiquitin HNF4a, MYCN Ubiquitin, CDKN1B, SNCA  –3.12  
PTEN
 
Phosphatase and tensin homolog
 
BCL2, CASP3, TNFRSF6, AKT1, CSN2
 
ERBB2, BCL2, TGFB1, HBX, EGR1
 
MAGI-3, AIP1, TXN, p53
 
–3.90
 

Twenty genes, identified for further analysis from 5 networks using the Ingenuity Analysis software, had lower average expression in patients with AL (or higher average expression in patients with MM). The table is a partial list of dynamic interactions between these 20 focus genes and other genes that critically influence the function of the focus genes. The value of the test statistic is shown as a comparison of AL and MM plasma cells.

*

Genes in these rows may be particularly relevant to the pathogenesis of AL and MM, including MYC, p53, E2A, XRCC5 (Ku 80), IL6-ST, CASP3, and CDK4

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