Synergistic Effect of Venetoclax and Bendamustine in Early T-cell Precursor Acute Lymphoblastic Leukemia.
In Vivo
; 38(4): 1740-1749, 2024.
Article
em En
| MEDLINE
| ID: mdl-38936885
ABSTRACT
BACKGROUND/AIM:
To date, therapeutic options for T-cell acute lymphoblastic leukemia (T-ALL) remain very limited. This study evaluated the efficacy of monotherapies and combination therapies including a selective BCL-2 inhibitor for T-ALL cell lines, namely Jurkat, CCRF-CEM, and Loucy. MATERIALS ANDMETHODS:
Loucy is an early T-precursor ALL (ETP-ALL) cell line characterized by an immature phenotype, whereas Jurkat and CCRF-CEM are late T-cell progenitor ALL (LTP-ALL) cell lines. Monotherapy was conducted with venetoclax, cytarabine, bendamustine, or azacytidine, whereas combination therapy was performed with venetoclax plus cytarabine, venetoclax plus bendamustine, or venetoclax plus azacytidine. Cell viability assay was conducted after 48 h using Trypan blue and the 3-(4, 5-dimethylthiazol-2-yl)-5-(3-carboxymethoxyphenyl)-2-(4-sulfophenyl)-2H-tetrazolium (MTS). Statistical analysis for evaluating synergistic interactions between anticancer drugs was performed by using the SynergyFinder Plus and drc R package.RESULTS:
Adding venetoclax to cytarabine, bendamustine, or azacitidine achieved an additive effect, with Loewe synergic scores ranging from -10 to 10 in Jurkat and CCRF-CEM. Conversely, the combination of venetoclax and cytarabine displayed an additive effect (Loewe synergic score 8.45 and 5.82 with MTS and Trypan blue assays, respectively), whereas venetoclax plus bendamustine or azacitidine exhibited a synergistic effect (Loewe synergic score >10 with MTS assay) in Loucy. Remarkably, the Bliss/Loewe score revealed that the combination of venetoclax and bendamustine was the most synergistic, yielding a score of 13.832±0.55.CONCLUSION:
The combination of venetoclax and bendamustine demonstrated the greatest synergistic effect in suppressing ETP-ALL cell proliferation. Further studies are warranted to determine the mechanisms for the synergism between venetoclax and bendamustine in high-risk T-ALL.Palavras-chave
Texto completo:
1
Coleções:
01-internacional
Temas:
Geral
/
Tipos_de_cancer
/
Leucemia
Base de dados:
MEDLINE
Assunto principal:
Sulfonamidas
/
Protocolos de Quimioterapia Combinada Antineoplásica
/
Compostos Bicíclicos Heterocíclicos com Pontes
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Sinergismo Farmacológico
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Leucemia-Linfoma Linfoblástico de Células T Precursoras
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Cloridrato de Bendamustina
Limite:
Humans
Idioma:
En
Revista:
In Vivo
/
In Vivo (Online)
Assunto da revista:
NEOPLASIAS
Ano de publicação:
2024
Tipo de documento:
Article