Artículo
Apoptotic regulator BCL-2 blockade aS a potential therapy in classical Hodgkin Lymphoma
Gamboa Cedeño, Angélica María; Díaz, Mariángeles
; Cristaldo, Nancy; Otero, Victoria; Schutz, Natalia; Fantl, Dorotea; Cugliari, María Silvana; Zerga, Marta Elisa; Rojas Bilbao, Érica; Jauk, Federico; Garcia Rivello, Hernan Jorge; Núñez, Myriam Carmen; Ranuncolo, Stella Maris
Fecha de publicación:
03/2021
Editorial:
Pergamon-Elsevier Science Ltd
Revista:
Life Sciences
ISSN:
0024-3205
Idioma:
Inglés
Tipo de recurso:
Artículo publicado
Clasificación temática:
Resumen
The challenge in classical Hodgkin Lymphoma (cHL) management is the 30–40% of refractory/relapsed cases. Aims: 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. Main 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. Key findings: 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 (DFS) and overall survival (OS) (p = 0.002, p = 0.02 respectively). A decision tree analysis, in a 30 patients subgroup, showed that patients with <60% NIK+ HRS-cells but with ≥60% BCL-2+ HRS-cells had a worse outcome in terms of DFS and OS. These parameters performed better as prognosis indicators as compared to the diagnosis bone marrow status. 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. Significance: 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.
Palabras clave:
BCL-2
,
HODGKIN LYMPHOMA
,
PROGNOSIS
,
REFRACTORY DISEASE
,
RELAPSED DISEASE
,
VENETOCLAX
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Identificadores
Colecciones
Articulos(OCA HOUSSAY)
Articulos de OFICINA DE COORDINACION ADMINISTRATIVA HOUSSAY
Articulos de OFICINA DE COORDINACION ADMINISTRATIVA HOUSSAY
Citación
Gamboa Cedeño, Angélica María; Díaz, Mariángeles; Cristaldo, Nancy; Otero, Victoria; Schutz, Natalia; et al.; Apoptotic regulator BCL-2 blockade aS a potential therapy in classical Hodgkin Lymphoma; Pergamon-Elsevier Science Ltd; Life Sciences; 268; 118979; 3-2021; 1-12
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