Synergistic Effect of Venetoclax and Bendamustine in Early T-cell Precursor Acute Lymphoblastic Leukemia.

Autor:	Nguyen HDT; Department of Biomedical Science, Graduate School, Kyungpook National University, Daegu, Republic of Korea.; BK21 Four Program, School of Medicine, Kyungpook National University, Daegu, Republic of Korea., LE TM; Department of Biomedical Science, Graduate School, Kyungpook National University, Daegu, Republic of Korea.; BK21 Four Program, School of Medicine, Kyungpook National University, Daegu, Republic of Korea., Lee D; Department of Biomedical Science, Graduate School, Kyungpook National University, Daegu, Republic of Korea.; BK21 Four Program, School of Medicine, Kyungpook National University, Daegu, Republic of Korea., Cho HJ; Department of Hematology/Oncology, Kyungpook National University Hospital, School of Medicine, Kyungpook National University, Daegu, Republic of Korea., Lee J; Department of Hematology/Oncology, Kyungpook National University Chilgok Hospital, School of Medicine, Kyungpook National University, Daegu, Republic of Korea., Sohn SK; Department of Hematology/Oncology, Kyungpook National University Hospital, School of Medicine, Kyungpook National University, Daegu, Republic of Korea., Kim JG; Department of Hematology/Oncology, Kyungpook National University Chilgok Hospital, School of Medicine, Kyungpook National University, Daegu, Republic of Korea., Ham JY; Department of Laboratory Medicine, Kyungpook National University Chilgok Hospital, School of Medicine, Kyungpook National University, Daegu, Republic of Korea., Moon JH; Department of Hematology/Oncology, Kyungpook National University Chilgok Hospital, School of Medicine, Kyungpook National University, Daegu, Republic of Korea., Han HS; Department of Biomedical Science, Graduate School, Kyungpook National University, Daegu, Republic of Korea.; BK21 Four Program, School of Medicine, Kyungpook National University, Daegu, Republic of Korea., Kim J; Department of Hematology/Oncology, Kyungpook National University Chilgok Hospital, School of Medicine, Kyungpook National University, Daegu, Republic of Korea; dnakim1@gmail.com., Baek DW; Department of Hematology/Oncology, Kyungpook National University Chilgok Hospital, School of Medicine, Kyungpook National University, Daegu, Republic of Korea; baekdw83@gmail.com.
Jazyk:	angličtina
Zdroj:	In vivo (Athens, Greece) [In Vivo] 2024 Jul-Aug; Vol. 38 (4), pp. 1740-1749.
DOI:	10.21873/invivo.13624
Abstrakt:	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 and Methods: 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. (Copyright © 2024, International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.)
Databáze:	MEDLINE
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