STUDY OF AUTOPHAGY RESPONSE IN NEOPLASTIC CLL CELLS

Congreso; LXIV Reunión Anual de la SAI; 2016

Chronic Lymphocytic Leukemia (CLL) is a disease characterized by the clonal proliferation and accumulation of mature, typically CD5-positive B-cells within the blood, bone marrow, lymph nodes, and spleen. Leukemic transformation is initiated by alterations that impair apoptosis of clonal B-cells. The pathway engaged in 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 in cancer depending of the type of tumor cells. This mechanism can be 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 inhibitor) modulates B cell death induced by Fludarabin. We therefore, performed an analysis of LC3B expression to evaluate autophagy induction, in peripheral blood mononuclear cells (PBMC) isolated from CLL-patients. We stimulated PBMC with Rapamycin and observed an increased expression of LC3B II, which correlated with the level of cell death in a co-culture with Rapamycin and Fludarabin. Moreover, when we used another mTOR inhibitor (PP242) to stimulate PBMC, we observed higher levels of LC3B II compared to Rapamycin. These preliminary experiments are being assayed in others CLL patient samples and also we plan to evaluate cell death using PP242 plus Fludarabin. These preliminary results may provide important clues to define new strategies for leukemia therapy.Key words: mTOR inhibitors, Autophagy, Chronic Lymphocytic Leukemia