Gene expression of anti- and pro-apoptotic proteins in malignant and normal plasma cells.
The survival of malignant plasma cells is a key event in disease occurrence, progression and chemoresistance. Using DNA-microarrays, we analysed the expression of genes coding for 58 proteins linked with extrinsic and intrinsic apoptotic pathways, caspases and inhibitor of apoptosis proteins. We considered six memory B cells (MBC), seven plasmablasts (PPC), seven bone marrow plasma cells (BMPC) and purified myeloma cells (MMC) from 92 newly-diagnosed patients. Forty out of the 58 probe sets enabled the separation of MBC, PPC and BMPC in three homogeneous clusters, characterized by an elevated expression of TNFRSF10A, TNFRSF10B, BCL2A1, CASP8, CASP9 and PMAIP1 genes for MBC, of FAS, FADD, AIFM1, BIRC5, CASP CASP2, CASP3 and CASP6 for PPC and of BCL2, MCL1, BID, BIRC3 and XIAP for BMPC. Thus, B cell differentiation was associated with change of expression of pro-apoptotic and anti-apoptotic genes. Regarding MMC, the major finding was TRAIL upregulation that might be counteracted by a high osteoprotegerin production by BM stromal cells and a decreased expression of FAS, APAF1 and BNIP3 compared to normal BMPC. Out of the 40 genes, CASP2 and BIRC5 expression in MMC had adverse prognosis in two independent series of previously-untreated patients.
Jourdan
Michel
M
INSERM U847, Equipe Labellisée LIGUE 2006, Montpellier, France.
Reme
Thierry
T
Goldschmidt
Hartmut
H
Fiol
Geneviève
G
Pantesco
Véronique
V
De Vos
John
J
Rossi
Jean-François
JF
Hose
Dirk
D
Klein
Bernard
B
D017209:Apoptosis / Q000235:genetics; D051017:Apoptosis Regulatory Proteins / Q000235:genetics*; D053143:Caspase 2 / Q000235:genetics; D020169:Caspases / Q000235:genetics; D002454:Cell Differentiation; D002470:Cell Survival / Q000235:genetics; D003546:Cysteine Endopeptidases / Q000235:genetics; D020869:Gene Expression Profiling / Q000379:methods; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D007156:Immunologic Memory / Q000235:genetics; D051034:Inhibitor of Apoptosis Proteins / Q000235:genetics*; D008869:Microtubule-Associated Proteins / Q000235:genetics; D009101:Multiple Myeloma / Q000235:genetics* / Q000378:metabolism; D020411:Oligonucleotide Array Sequence Analysis; D010950:Plasma Cells / Q000378:metabolism*; D025341:Principal Component Analysis; D011379:Prognosis; D020133:Reverse Transcriptase Polymerase Chain Reaction / Q000379:methods; D018709:Statistics, Nonparametric; D000077022:Survivin
D051017:Apoptosis Regulatory Proteins; C107489:BIRC5 protein, human; D051034:Inhibitor of Apoptosis Proteins; D008869:Microtubule-Associated Proteins; D000077022:Survivin; C490360:CASP2 protein, human; D053143:Caspase 2; D020169:Caspases; D003546:Cysteine Endopeptidases