IRIBARREN PABLO
Congresos y reuniones científicas
Título:
TLR2 stimulation promotes autophagy and modulates fludarabine-induced cell death in chronic lymphocytic leukemia cells.
Autor/es:
ARROYO, DS; BUSSI, C; PERALTA RAMOS, JAVIER MARÍA; RODRIGUEZ, CM; IRIBARREN, P
Reunión:
Congreso; Reunión conjunta de sociedades de Biociencias (SAI); 2017
Institución organizadora:
Sociedades de Biociencias, Argentina
Resumen:
?TLR2 STIMULATION PROMOTES AUTOPHAGY AND MODULATES FLUDARABINE-INDUCED CELL DEATH IN CHRONIC LYMPHOCYTIC LEUKEMIA CELLS? 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.