Abstract 353: Investigate the role of homoharringtonine in treating B-cell acute lymphoblastic leukemia

Abstract

<p>B lymphoblastic leukemia (B-ALL) is an aggressive and highly lethal hematolymphoid malignancy and it is the most common cancer in children. Although the incidence of B-ALL in adult is lower than that in children, adult patients with B-ALL have a poor prognosis. Relapse/refractory disease is still the main cause of death in B-ALL patients. Homoharringtonine (HHT) is a plant alkaloid that was approved to treat chronic myeloid leukemia (CML) by FDA. Herein, we aimed to investigate the anti-leukemic activity of HHT in B-ALL. Cell viability was reduced in a time and dose-dependent manner upon treatment with HHT. Moreover, HHT was able to induce apoptosis in B-ALL cell lines by downregulating the MCL-1 protein level after 24 hours of treatment. Cell cycle analysis indicated G1 phase arrest, and western blot analysis demonstrated downregulation of CDK-4 and CDK-6. A proteomics study using label-free protein quantitation revealed enrichment of proteins involved in fatty acid oxidation, and further analysis showed downregulation of acyl-CoA desaturase after HHT treatment. Additionally, HHT significantly reduced the leukemic burden and prolonged survival in NSG mice injected with the PALL-2 cell line. Overall, the findings suggest that HHT is effective in treating B-ALL by inducing cell cycle arrest, with a potential inhibitory effect on fatty acid oxidation. Further studies will be conducted to evaluate the mechanism of modulation of fatty acid oxidation.<br></p>