Identificación de marcadores moleculares predictivos de refractariedad y recaída en pacientes con linfoma de Hodgkin clásico.

GAMBOA-CEDEÑO, ANGÉLICA MARÍA; OTERO, VICTORIA; SCHUTZ, NATALIA; FANTL, DOROTEA; GARCIA-RIVELLO, HERNÁN; JAUK, FEDERICO; RANUNCOLO, STELLA MARIS

CABA

Jornada; Jornadas de Investigación del Hospital Italiano de Buenos Aires.; 2017

Hospital Italiano de Buenos Aires (HIBA)

Background. The challenge in classical Hodgkin Lymphoma (cHL) management is the 30-40% of refractory/relapsed cases.Objectives. The aim of this work was to determine whether, NIK and BCL-2, could be useful as prognosis biomarkers in cHL. In addition, we evaluated BCL-2 as a directed-therapy in cHL cell lines using venetoclax. Methods. We evaluated NIK and BCL-2 expression in 112 untreated cHL patients? lymph-node biopsies by immunohistochemistry. cHL cell lines were treated with venetoclax alone or combined with vincristine or doxorubicin. Cell viability, metabolic activity and cell death were analyzed by trypan-blue exclusion method, MTS assay and FDA/IP staining respectively. Results. No correlation between NIK or BCL-2 expression and the majority of the clinical parameters was found. Patients with ≥60% BCL-2+ HRS-cells had a shorter disease-free survival and overall survival (p=0.002, p=0.02 respectively). Human cHL cell lines U-H01, KM-H2, L1236, SUPHD1, L540 showed sensitivity to venetoclax. The co-treatment effect of venetoclax and vincristine or doxorubicin on cell viability was diverse depending on the cell line evaluated. Conclusions. BCL-2 should be considered as a prognosis biomarker as well as a potential new therapeutic target in cHL. We report for the first time the cytotoxic effect of venetoclax in human cHL cell lines.