INNATE IMMUNE RECEPTORS MODULATE AUTOPHAGY AND CHEMOTHERAPEUTIC DRUGS-INDUCED CELL DEATH IN CHRONIC LYMPHOCYTIC LEUKEMIA

BAEZ, NATALIA S; IRIBARREN, PABLO; RODRIGUEZ CECILIA M; HELLER VIVIANA B; ARROYO DANIELA S; MANZONE-RODRIGUEZ CLARISA

San Miguel de Tucumán

Congreso; LXVII Reunión Anual de la Sociedad Argentina de Inmunología; 2019

Chronic Lymphocytic Leukemia (CLL) is characterized by the accumulation of mature, clonal B lymphocytes (BL) in the peripheral blood, bone marrow and lymphoid organs. Emerging evidence suggests that Toll-like receptors (TLRs) activation is involved in the pathogenesis of progressive CLL. However, heterogeneous response to TLR activation was observed in different subgroups of CLL cases, depending on biological and clinical features and the TLR family member stimulated. Previously we reported that TLR2 stimulation promoted phagocyte cell death in an autophagy-dependent manner. Particularly in CLL, autophagy can be a key factor because it is regulated by proteins that also control cell death, which is altered in this disease.The aim of this work is to study whether the stimulation of TLR2 or NOD2 (another innate immune receptor) regulates autophagy and survival of CLL-BL in the presence or absence of the chemotherapeutic drugs Fludarabine or ABT-199. Peripheral blood mononuclear cells from CLL patients, were stimulated with Pam3CSK4 (TLR2 ligand) or MDP (NOD2 ligand) in the presence or absence of Fludarabine and ABT-199 and cultured by different times. Then, we determined cell death frequency by flow cytometry and autophagy markers expression by western blott.Pam3CSK4 modulated fludarabine-induced cell death and increased the expression of LC3BII and p62. On the other hand, MDP induced similar effects on the expression of autophagy proteins and modulated ABT-199 induced cell death.These preliminary results suggest that stimulation of these innate immunity receptors may regulate CLL cells responses associated to disease progression.