Recurrent 11q24.3 gain contributes to the pathogenesis of diffuse large B cell lymphoma by deregulating ETS1 and FLI1

Diplôme Thèse Recurrent 11q24.3 gain contributes to the pathogenesis of diffuse large B cell lymphoma by deregulating ETS1 and FLI1 eng 2014-05-13 author Testoni Monica 743188 director Scapozza Leonardo 600318 director Bertoni Francesco 10.13097/archive-ouverte/unige:39207 urn:nbn:ch:unige-392076 Sc. 4669 DLBCL is the most frequent and aggressive form of non-Hodgkin's lymphoma. The still high percentage of mortality is in part due to the heterogeneity of DLBCL at genetic level. Among genetic alterations, a recurrent gain at 11q24.3 was detected in 26% of DLBCL. It was associated with higher expression of ETS1 and FLI1 transcription factors. Silencing of both genes led to cell death and a block in proliferation in a DLBCL cell line bearing the specific 11q gain but only FLI1 silencing gave a similar phenotype in cell lines without the gain. At molecular level, ETS1 directly and negatively regulates BLIMP1 expression. Importantly, ETS1 or FLI1 silencing leads to changes in the expression of B cell important genes. This project reveals ETS1 and FLI1 as interesting drug targets to be further analyzed. In addition, the status of MYC gene was analyzed in this cohort of DLBCL patients treated with R-CHOP. Dewey 615 31 Section des sciences pharmaceutiques 17 false 184d72a2-9a9d-4c71-835e-673ca132b5be Thesis Public TesiDefinitiva_Monica.pdf 6736119 application/pdf a4717928-5b71-4e86-9010-86aa17c6fc14 Appendix Public Appendix tables_TestoniMonica.pdf 2027610 application/pdf openAccess Faculté des sciences / Section des sciences pharmaceutiques

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Recurrent 11q24.3 gain contributes to the pathogenesis of diffuse large B cell lymphoma by deregulating ETS1 and FLI1				2014	1,024	1,459

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Testoni, Monica