title: SAGE analysis demonstrates increased expression of TOSO contributing to Fas-mediated resistance in CLL.
abstract: 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.
authors.affiliation: Hematology Division and Center for Cell-Based Therapy, Faculty of Medicine of Ribeirão Preto, University of São Paulo, São Paulo, Brazil.
authors.forename: Rodrigo
authors.initials: R
authors.lastname: Proto-Siqueira
authors.forename: Rodrigo A
authors.initials: RA
authors.lastname: Panepucci
authors.forename: Francisco P
authors.initials: FP
authors.lastname: Careta
authors.forename: Abigail
authors.initials: A
authors.lastname: Lee
authors.forename: Andrew
authors.initials: A
authors.lastname: Clear
authors.forename: Kelly
authors.initials: K
authors.lastname: Morris
authors.forename: Carolyn
authors.initials: C
authors.lastname: Owen
authors.forename: Edgar G
authors.initials: EG
authors.lastname: Rizzatti
authors.forename: Wilson A
authors.initials: WA
authors.lastname: Silva
authors.forename: Roberto P
authors.initials: RP
authors.lastname: Falcão
authors.forename: Marco A
authors.initials: MA
authors.lastname: Zago
authors.forename: John G
authors.initials: JG
authors.lastname: Gribben
mesh_terms: 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
chemical_list: D051017:Apoptosis Regulatory Proteins; C112037:FCMR protein, human; D008565:Membrane Proteins; D019014:fas Receptor