Apoptotic regulator BCL-2 blockade as a potential therapy in classical Hodgkin Lymphoma.
Life Sci
; 268: 118979, 2021 Mar 01.
Article
em En
| MEDLINE
| ID: mdl-33421528
ABSTRACT
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. MAINMETHODS:
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. KEYFINDINGS:
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.Palavras-chave
Texto completo:
1
Coleções:
01-internacional
Temas:
Geral
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Tipos_de_cancer
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Outros_tipos
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Tratamento
Base de dados:
MEDLINE
Assunto principal:
Sulfonamidas
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Doença de Hodgkin
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Compostos Bicíclicos Heterocíclicos com Pontes
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Proteínas Proto-Oncogênicas c-bcl-2
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Antineoplásicos
Tipo de estudo:
Prognostic_studies
Limite:
Adolescent
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Adult
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Aged
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Child
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Female
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Humans
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Male
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Middle aged
Idioma:
En
Revista:
Life Sci
Ano de publicação:
2021
Tipo de documento:
Article
País de afiliação:
Argentina