Autologous T cell activation fosters ABT-199 resistance in chronic lymphocytic leukemia (CLL) and selects malignant cells with an aggressive phenotype.

COLADO, ANA; RISNIK, DENISE; CUSTIDIANO, MARÍA DEL ROSARIO; GARATE, GONZALO MARTÍN; GAMBERALE, ROMINA; ELÍAS, ESTEBAN ENRIQUE; CORDINI, GREGORIO; BEZARES, RAIMUNDO FERNANDO; VICENTE, ÁNGELES; GIORDANO, MIRTA; VERGARA-RUBIO, MARICEF; FERNÁNDEZ-GRECCO, HORACIO; SÁNCHEZ-ÁVALOS, JULIO CÉSAR; BORGE, MERCEDES

Mar del Plata

Congreso; LXVI Reunión Anual de la Sociedad Argentina de Inmunología 2018; 2018

Sociedad Argentina de Inmunología

BCR signaling and activated T cells from the microenvironment favor malignant cell activation, proliferation and survival in CLL. ABT-199, a specific BCL-2 inhibitor, is highly cytotoxic against unstimulated CLL cells. We reported that T cell activation induces ABT-199 resistance in CLL cells (Elías-Haematologica-2018). To further characterize resistant CLL cells, PBMC from CLL patients were cultured for 48hs without (control) or with anti-CD3 (aCD3) to activate T cells, and then ABT-199 was added to the cultures. Leukemic cell survival, activation and proliferation capacity were evaluated by flow cytometry. While control CLL cells treated with ABT-199 showed more than 93% of cell death after 48hs of ABT-199 treatment, CLL cells from aCD3 cultures are still alive with ABT-199 at 120hs (%CD19+ viable cells: 63±8 vs 34±7 for aCD3 vs aCD3+ABT-199) and show similar levels of the activation marker CD86 (n=9). Interestingly, CLL cells in aCD3+ABT-199 cultures showed increased size (n=9, p