This research project focuses on the role of a regulator of DNA methylation, whose activity is normally restricted to neuronal tissue, in the pathogenesis of an aggressive malignant B lymphoma subtype, mantle cell lymphomas (CMLs). CML accounts for 5 % of non-Hodgkin malignant B lymphomas. The identification of causal mutations of cancer in CML remained elusive, making it difficult to develop rationalised therapies. In contrast, overall epigenetic disturbances, in particular DNA methylation, are described. Although mechanisms are not yet known, this indicates a key role of DNA methylation in the development and/or progression of LCMs. Following a proteomic study, our team revealed abnormal overexpression of a regulatory factor for DNA methylation in CML and large cell diffuse B lymphomas. Remarkably, this overexpression is not observed in painless lymphomas or normal B lymphoid cells suggesting a particular role of this factor in aggressive lymphomas. The REHETLYM project therefore proposes to study the pathogenic impact of the aberrant expression of this factor in CMLs, with the objective 1/d to identify new pathophysiological mechanisms of therapeutic interest in CML 2/d to evaluate the diagnostic and prognostic relevance of this factor in CML patients.