Abstract B02: Bortezomib-resistant pediatric acute myeloid leukemia cell lines derived from Down syndrome patients are sensitive to disulfiram (original) (raw)

Cancer Research, 2016

Abstract

Background: Acute myeloid leukemia (AML) continues to have an overall poor prognosis of about 50% in children. Treatment options for relapsed or refractory AML are limited. Bortezomib, a well-established proteasome inhibitor, is used in AML therapy. It binds to the beta 5 subunit (PSMB5) of the 26S proteasome and inhibits the chymotrypsin (CT)-like activity. Although patients develop resistance to bortezomib, the mechanism is not fully elucidated. Disulfiram (DS) is an aldehyde dehydrogenase (ALDH) inhibitor used to treat alcoholism without major side effects. DS has anticancer cytotoxicity that is in part copper (Cu2+)-dependent (DS/Cu2+). One of the reported mechanisms of action of DS is through proteasome inhibition. We previously demonstrated that both DS/Cu2+ and bortezomib are cytotoxic in a panel of AML cell lines. In the present study, we focused on two acute megakaryoblastic leukemia cell lines derived from patients with Down syndrome (CMY and CMK), one of the cell lines is...

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