SAGE analysis demonstrates increased expression of TOSO contributing to Fas-mediated resistance in CLL.
To identify novel genes involved in the molecular pathogenesis of chronic lymphocytic leukemia (CLL) we performed a serial analysis of gene expression (SAGE) in CLL cells, and compared this with healthy B cells (nCD19(+)). We found a high level of similarity among CLL subtypes, but a comparison of CLL versus nCD19(+) libraries revealed 55 genes that were over-represented and 49 genes that were down-regulated in CLL. A gene ontology analysis revealed that TOSO, which plays a functional role upstream of Fas extrinsic apoptosis pathway, was over-expressed in CLL cells. This finding was confirmed by real-time reverse transcription-polymerase chain reaction in 78 CLL and 12 nCD19(+) cases (P < .001). We validated expression using flow cytometry and tissue microarray and demonstrated a 5.6-fold increase of TOSO protein in circulating CLL cells (P = .013) and lymph nodes (P = .006). Our SAGE results have demonstrated that TOSO is a novel over-expressed antiapoptotic gene in CLL.
Proto-Siqueira
Rodrigo
R
Hematology Division and Center for Cell-Based Therapy, Faculty of Medicine of Ribeirão Preto, University of São Paulo, São Paulo, Brazil.
Panepucci
Rodrigo A
RA
Careta
Francisco P
FP
Lee
Abigail
A
Clear
Andrew
A
Morris
Kelly
K
Owen
Carolyn
C
Rizzatti
Edgar G
EG
Silva
Wilson A
WA
Falcão
Roberto P
RP
Zago
Marco A
MA
Gribben
John G
JG
D051017:Apoptosis Regulatory Proteins / Q000235:genetics* / Q000502:physiology; D020869:Gene Expression Profiling / Q000379:methods*; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D015451:Leukemia, Lymphocytic, Chronic, B-Cell / Q000209:etiology* / Q000235:genetics / Q000473:pathology; D008565:Membrane Proteins / Q000235:genetics* / Q000502:physiology; D019014:fas Receptor
D051017:Apoptosis Regulatory Proteins; C112037:FCMR protein, human; D008565:Membrane Proteins; D019014:fas Receptor