Study of autophagy response in neoplastic CLL cells

RODRIGUEZ, CM; IRIBARREN, P; ARROYO, DS; PERALTA RAMOS, JM; BUSSI, C

Mar del Plata

Congreso; LXIV reunion anual. Sociedad Argentina de Inmunologia (SAI) SAIC; 2016

SAI -SAIC

Chronic Lymphocytic Leukemia (CLL) is a disease characterizedby the clonal proliferation and accumulation of mature, typicallyCD5-positive B-cells within the blood, bone marrow, lymphnodes, and spleen. Leukemic transformation is initiated by alterationsthat impair apoptosis of clonal B-cells. The pathway engagedin programmed cell death involves several Bcl-2 family proteins.Alternatively, Bcl-2?family proteins have antiautophagic function.In this regard, the autophagy response has dual phenotype incancer depending of the type of tumor cells. This mechanism canbe used for prolonging survival, or for cell death, as well. However,little is known the role of this degradative process in CLL-B cells.In previously studies, we observed that Rapamycin (mTOR inhibi -tor) modulates B cell death induced by Fludarabin. We therefore,performed an analysis of LC3B expression to evaluate autophagyinduction, in peripheral blood mononuclear cells (PBMC) isolatedfrom CLL-patients. We stimulated PBMC with Rapamycin andobserved an increased expression of LC3B II, which correlatedwith the level of cell death in a co-culture with Rapamycin andFludarabin. Moreover, when we used another mTOR inhibitor(PP242) to stimulate PBMC, we observed higher levels of LC3BII compared to Rapamycin. These preliminary experiments arebeing assayed in others CLL patient samples and also we plan toevaluate cell death using PP242 plus Fludarabin. These preliminary results may provide important clues to define new strategiesfor leukemia therapy