KEY TAKEAWAYS
- The study aimed to investigate the efficacy of venetoclax and bendamustine, alone and in combination, in suppressing T-ALL cell proliferation.
- Researchers noticed a significant synergistic effect of venetoclax and bendamustine in suppressing patients with ETP-ALL cell proliferation.
To date, therapeutic options for patients with T-cell acute lymphoblastic leukemia (T-ALL) remain very limited.
Hong Duc Thi Nguyen and the team aimed to evaluate the efficacy of monotherapies and combination therapies, including a selective BCL-2 inhibitor, for T-ALL cell lines, namely Jurkat, CCRF-CEM, and Loucy.
They performed an inclusive analysis using Loucy, an early T-precursor ALL (ETP-ALL) cell line characterized by an immature phenotype, and Jurkat and CCRF-CEM, which are late T-cell progenitor ALL (LTP-ALL) cell lines. Monotherapy treatments included venetoclax, cytarabine, bendamustine, or azacytidine, while combination therapies involved venetoclax + cytarabine, venetoclax + bendamustine, or venetoclax + azacytidine.
Cell viability was assessed after 48 hours using Trypan blue and the 3-(4, 5-dimethylthiazol-2-yl)-5-(3-carboxymethoxyphenyl)-2-(4-sulfophenyl)-2H-tetrazolium (MTS) assay. Statistical analysis to evaluate synergistic interactions between anticancer drugs was conducted using SynergyFinder + and the drc R package.
By 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 + 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.
The study concluded that 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.
This research was supported by a grant of the Korea Health Technology R&D Project through the Korea Health Industry Development Institute (KHIDI), funded by the Ministry of Health & Welfare, Republic of Korea.
Source: https://pubmed.ncbi.nlm.nih.gov/38936885/
Nguyen HDT, LE TM, Lee D, et al. (2024). “Synergistic Effect of Venetoclax and Bendamustine in Early T-cell Precursor Acute Lymphoblastic Leukemia.” In Vivo. 2024 Jul-Aug;38(4):1740-1749. doi: 10.21873/invivo.13624. PMID: 38936885.
