Autologous T cell activation fosters ABT-199 resistance in CLL and selects malignant cells with an aggressive phenotype

ELIAS E; COLADO A; FERNANDEZ GRECCO H.; CUSTIDIANO, MARÍA DEL ROSARIO; BEZARES RF; SANCHEZ AVALOS J; BORGE M; GIORDANO M; - GAMBERALE R

Congreso; LXVI Annual Meeting of Sociedad Argentina de Inmunología; 2018

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 previously reported that T cell activation induces ABT-199 resistance in CLL cells (Elías-Haematologica-2018). To further characterize resistant CLL cells, peripheral blood mononuclear cells 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 at different times. 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). Moreover, CLL cells in aCD3+ABT-199 cultures showed increased size (n=9, p