Abstract 1574: Homoharringtonine is effective in treating acute lymphoblastic leukaemia via modulation of apoptotic pathway

Abstract

Abstract Acute lymphoblastic leukaemia (ALL) is an aggressive and highly lethal malignancy caused by clonal mutations in lymphoid progenitor cells. The prognosis for adult ALL remains poor, with only 30-40% of adult patients achieving long-term remission. Therefore, novel therapies are needed. Homoharringtonine (HHT) is a natural-derived plant alkaloid from tree of Cephalotaxus. FDA approved the use of HHT in the treatment of chronic myeloid leukaemia (CML) in 2012. Limited pre-clinical or clinical studies were conducted for therapeutic efficacy and molecular mechanisms of HHT on ALL to the best of our knowledge. To fill this knowledge gap, here we investigated the antileukemic activity of HHT in T lymphoblastic leukaemia (T-ALL) and B lymphoblastic leukaemia (B-ALL). In this study, T-ALL cell lines namely JURKAT, MOLT-4, LOUCY, CCRF-CEM and B-ALL cell clines namely PALL-2, SUP-B15 were used. Cell viability was reduced upon treatment of HHT at time and dose-dependent manner. Percentage of apoptotic cells that determined by flow cytometric analysis of PI and Annexin V double staining was increased upon treatment of HHT. Moreover, HHT was able to induce apoptosis in both T-ALL and B-ALL cell lines. Western blot analysis showed that MCL-1 protein level was reduced upon treating with HHT for 24 hours. The above findings provide conclusive evidence for the therapeutic effect of HHT on various ALL cell lines by modulating the apoptotic pathway. Citation Format: Anan Jiao, Kei Ching Yuen, Rahman Ud DIN, On Yi Phoebe Wong, Sin Chun-Fung. Homoharringtonine is effective in treating acute lymphoblastic leukaemia via modulation of apoptotic pathway [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2023; Part 1 (Regular and Invited Abstracts); 2023 Apr 14-19; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2023;83(7_Suppl):Abstract nr 1574.