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SAGE analysis demonstrates increased expression of TOSO contributing to Fas-mediated resistance in CLL

By Rodrigo Proto-Siqueira, Rodrigo A. Panepucci, Francisco P. Careta, Abigail Lee, Andrew Clear, Kelly Morris, Carolyn Owen, Edgar G. Rizzatti, Wilson A. Silva, Roberto P. Falcão, Marco A. Zago and John G. Gribben


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

Topics: Neoplasia
Publisher: American Society of Hematology
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Provided by: PubMed Central
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