Hairy cell leukemia: in vitro sensitivity to venetoclax and role of the microenvironment.

ALEXIA VEREERTBRUGGHEN; MARICEF VERGARA RUBIO; BEZARES FERNANDO; BORGE MERCEDES; MORANDE, PABLO E; ELÍAS ESTEBAN ENRIQUE; AMONDARAIN, MIKELE; CORDINI, GREGORIO; GIORDANO MIRTA; ANA COLADO; SARAPURA MARTÍNEZ, VALERIA; FERNÁNDEZ GRECCO HORACIO; GAMBERALE ROMINA

San Miguel de Tucumán

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

SAI

Background:Hairy cell leukemia (HCL) is a neoplastic disease of low incidence that affects the elderly and is characterized by the accumulation of tumor B cells in spleen, bone marrow and peripheral blood. Pancytopenia represents the most frequent symptom and although treatment with purine analogs shows a partial response, it remains incurable. Venetoclax is a Bcl-2 inhibitor successfully used in chronic lymphocytic leukemia (CLL). Given that HCL cells express Bcl-2, our aim was to evaluate venetoclax in vitro, as a potential therapy for HCL.Methods:Peripheral blood mononuclear cells from HCL patients were incubated with venetoclax, and after 24 hs apoptosis was evaluated by flow cytometry using AnnexinV. Because microenvironment signals induce resistance to venetoclax in CLL, we also evaluated the effect of the drug in HCL cells pre-incubated with agonists for TLR-9 (CpG), or TLR-2 (PAM3), or anti-CD3-activated T cells.Results:Venetoclax increased the percentages of AnnexinV+ HCL cells at clinically relevant concentrations of 0.1 and 1 µM (n=5, p