TLR2 STIMULATION INCREASES LC3B II LEVELS AND MODULATES FLUDARABINE-INDUCED CELL DEATH IN CHRONIC LYMPHOCYTIC LEUKEMIA CELLS

ARROYO, DS; BUSSI, C; PERALTA RAMOS, JAVIER M.; HELLER, VB; RODRIGUEZ, CM; IRIBARREN, P

Conferencia; Buenos Aires Research Conferences on Autophagy; 2017

?TLR2 STIMULATION INCREASES LC3B II LEVELS AND MODULATES FLUDARABINE-INDUCED CELL DEATH IN CHRONIC LYMPHOCYTIC LEUKEMIA CELLS? Authors: Daniela S. Arroyo1,2, Claudio Bussi2, Javier M. Peralta Ramos2, Viviana B. Heller1, Cecilia M. Rodriguez1,2 and Pablo Iribarren2 E-mail: daniarroyo@fcq.unc.edu.ar1 Laboratorio de Oncohematología del Hospital Nacional de Clínicas y 2 Dpto. Bioquímica Clínica, CIBICI-CONICET, Facultad de Ciencias Químicas, Universidad Nacional de Córdoba, Córdoba, Argentina.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 and the pathways engaged in programmed cell death involve several Bcl-2 family proteins. It has been described that Bcl-2?family proteins may regulate autophagy. This degradative pathway has dual role in cancer depending of the type of tumor. Therefore, autophagy can be exploited for promote survival, or cell death, as well. Whereas autophagy can be regulated by Toll like receptors (TLRs), and these receptors participate in the CLL progressive pathogenesis, we hypothesize that TLR2 activation modulate autophagy in CLL cells. This effect may influence the expression of genes and proteins involved in CLL pathogenesis. We analyzed LC3B expression in peripheral blood mononuclear cells isolated from CLL-patients. Pam3CSK4 (TLR2 ligand) induced increased LC3B II expression in CLL cells and this effect was potentiated by co-stimulation with Pam3CSK4 plus Fludarabine. Interestingly, Pam3CSK4 modulated CLL cell death induced by Fludarabine. On the other hand, MDP (ligand for the innate immunity receptor NOD2) induced similar effects on CLL cells. These preliminary results suggest that innate receptors may affect autophagy and leukemia cell survival.