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Master Thesis

Évaluation de différents facteurs pronostiques dans les lymphomes B diffus a grandes cellules traités par R-CHOP

Abstract : Diffuse Large B-Cell Lymphoma (DLBCL) is a clinically heterogeneous hematological cancer. Standard first line immunochemotherapy (R-CHOP) cure about 60% of fit patients. Despite extensive clinical, biological and molecular investigations, there is still no specific procedure to accurately discriminate refractory/relapse (R/R) DLBCL cases. On the one hand, overexpression of c-MYC or p53 is frequently found in DLBCL, but its association with prognosis remains controversial. On the other hand, CYCLON, a novel nuclear germline factor overexpressed in aggressive B-Cell Lymphoma, has been related to anti CD20 resistance in vitro. The aim of this study is to explore the expression of these biomarkers and their correlation with outcomes, clinical or pathological features. We established a retrospective cohort of 97 de novo DLBCL treated by R-CHOP. In univariate analysis, p53 overexpression (p53high) was associated with unfavorable outcomes and multivariate assessment showed that presence of a “starry-sky” pattern was correlated with better survival in p53high and/or c-MYC-positive DLBCL. NGS data revealed that these variables were associated with a specific mutational profile involved in cell survival. Atypical localizations of CYCLON and NPM1, an associated oncoprotein, were both strongly associated with progression free survival. Multivariate analyses showed that these atypical localizations of CYCLON and NPM1 were statistically significant and independent prognostic factors that add to the revised Index Prognosis (R-IPI) score for risk stratification by identifying DLBCL with especially worse prognosis. Altogether, we identified several potential druggable targets in DLBCL.
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Master Thesis
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https://dumas.ccsd.cnrs.fr/dumas-03332298
Contributor : Jean-Hugues Morneau Connect in order to contact the contributor
Submitted on : Tuesday, September 21, 2021 - 9:10:54 AM
Last modification on : Thursday, September 23, 2021 - 3:21:13 AM

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  • HAL Id : dumas-03332298, version 1

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Antonin Bouroumeau. Évaluation de différents facteurs pronostiques dans les lymphomes B diffus a grandes cellules traités par R-CHOP. Médecine humaine et pathologie. 2020. ⟨dumas-03332298⟩

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