Lipoprotein lipase expression in unmutated CLL patients is the consequence of a demethylation process induced by the microenvironment.

P. Moreno (1, 2) , C. Abreu (1) , M. Borge (3) , F. Palacios (1) , P. Morande (3) , M. Pegazzano (1) , S. Bianchi (1) , A. I. Landoni (4) , R. Agrelo (1) , M. Giordano (3) , G. Dighiero (1) , R. Gamberale (3) , P. Oppezzo (1, 5)

1 Institut Pasteur de Montevideo
2 Molecular Virology Laboratory, School of Science
3 IMEX - Instituto de Medicina Experimental
4 Service of Hematology and Bone Marrow Transplantation
5 mmunobiology Department, School of Medicine

ABSTRACT Among different prognostic factor in Chronic Lymphocytic Leukemia (CLL), we previously demonstrated that lipoprotein lipase (LPL) is associated to an unmutated (Um) immunoglobulin profile and clinical poor outcome. Despite the usefulness of LPL for CLL prognosis, its functional role and the molecular mechanism regulating its expression still open questions. Interaction of CLL B-cells with tissue microenvironment favors disease progression by promoting malignant B-cell growth. Since tissue methylation can be altered by environmental factors, we investigated the methylation status of LPL gene and the possibility that its over-expression could be associated to microenvironment signals. Our results show that a demethylated state of the LPL gene is responsible for its anomalous expression in Um CLL cases and that it expression is dependent of microenvironment signals. Overall, this work proposes that an epigenetic mechanism, triggered by the microenvironment, regulate LPL expression in CLL disease. KEYWORDS: CLL; LPL prognostic marker; Microenvironment; Methylation.

Domaines: Sciences du Vivant [q-bio]

P. Moreno, C. Abreu, M. Borge, F. Palacios, P. Morande, et al.. Lipoprotein lipase expression in unmutated CLL patients is the consequence of a demethylation process induced by the microenvironment.. Leukemia, 2013, 27 (3), pp.721-5. ⟨10.1038/leu.2012.212⟩. ⟨pasteur-00839345⟩