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

MORENO PILAR; ABREU CECILIA; BORGE MERCEDES; MORANDE PABLO ELIAS; PEGAZZANO MARIANA; FLORENCIA PALACIOS; BIANCHI SERGIO; LANDONI ANA INES; AGRELO RUBEN; GIORDANO MIRTA; DIGHIERO GUILLERMO; GAMBERALE ROMINA; OPPEZZO PABLO

LEUKEMIA

NATURE PUBLISHING GROUP

Lugar: Londres; Año: 2013 vol. 27 p. 721 - 725

0887-6924

The role that abnormal LPL expression could have in disease evolution, has been also addressed by previous work demonstrating that lipase-associated genes and triglyceride-specific lipase activity were increased when comparing CLL B cells to normal CD5+ B cells. Our results showing proliferation of the tumoral clone associated with demethylationand subsequent LPL expression support these results and highlight the idea that LPL gene could constitute a potential therapeutic target in Um CLL cases. By comparing methylation changes in the LPL-CpG island between Um and Mut CLL patients, we demonstrate a clearassociation between LPL expression and a demethylation process in the CpG island of the LPL gene. This process can be induced in the leukemic clone by specific microenvironment signals, delivered by CD40L/IL-4 and anti-IgM, but not by T-independent related signalsdelivered through Toll-like receptors. Overall, these results suggest that an epigenetic mechanism, triggered by the microenvironment, regulates LPL expression in CLL B cells.