Proteasome Inhibition by Carfilzomib Induced Apotosis and Autophagy in a T-cell Acute Lymphoblastic Leukemia Cell Line

T-cell acute lymphoblastic leukemia is an aggressive hematologic malignancy which is usuallyassociated with unfavorable prognosis particularly in patients with refractory/relapsed disease.Therefore, development of novel therapeutic strategies is highly required for improving theoutcome of these patients. Although there are several studies evaluating the efficacy of proteasomeinhibitors on acute lymphoblastic leukemia of B-cell lineage, the data are still limited regardingT-cell acute lymphoblastic leukemia. Here, we tried to investigate the effects of the proteasomeinhibition by carfilzomib on the induction of apoptosis and autophagy in Molt4 cells. The effectof carfilzomib in combination with dexamethasone in Molt4, as a glucocorticoid-resistant T-cellacute lymphoblastic leukemia cell line, was also assessed. Our data showed that carfilzomib caninduce both apoptosis and autophagy in Molt4 cells. Furthermore, we found that carfilzomib isa potent inducer of reactive oxygen species production and also induces G2/M phase cell cyclearrest in Molt4 cells. Concomitant treatment with carfilzomib and dexamethasone demonstratedthat carfilzomib can synergistically enhance the cytotoxic effect of dexamethasone on Molt4cells. Furthermore, co-treatment of the cells with carfilzomib and dexamethasone increasedthe induction of autophagy as compared with each drug alone. In conclusion, our results aresuggestive of the effectiveness of carfilzomib on Molt4 cells as a model of GC-resistant T-cellacute lymphoblastic leukemia.