Autologous T cell activation fosters ABT-199 resistance in chronic lymphocytic leukemia: rationale for a combined therapy with SYK inhibitors and anti-CD20 MoAbs.

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

HAEMATOLOGICA

FERRATA STORTI FOUNDATION

Año: 2018

0390-6078

Leukemic B cells from chronic lymphocytic leukemia (CLL) patients survive and proliferate within lymphoid tissues in contact with activated T cells, myeloid cells and receiving signals through the BCR. ABT-199 (venetoclax) is a potent, selective inhibitor of BCL-2 with promising clinical activity in CLL patients. ABT-199 rapidly induces apoptosis in unstimulated peripheral blood CLL cells in vitro, while CLL cells that have received survival signals from the microenvironment are less sensitive to the drug. In particular, signaling through the BCR or signals provided by fibroblast CD40L+ and by stromal cell lines were shown to reduce the sensitivity of CLL cells to ABT-199.In this study, we investigated whether resistance to ABT-199 can be conferred by autologous T cell activation, another important survival signal from the protective niches.