MTOR inhibition by everolimus in childhood acute lymphoblastic leukemia induces caspase-independent cell death.

ABSTRACT: Increasingly, anti-cancer medications are being reported to induce cell death mechanisms other than apoptosis. Activating alternate death mechanisms introduces the potential to kill cells that have defects in their apoptotic machinery, as is commonly observed in cancer cells, including in hematological malignancies. We, and others, have previously reported that the mTOR inhibitor everolimus has pre-clinical efficacy and induces caspase-independent cell death in acute lymphoblastic leukemia cells. Furthermore, everolimus is currently in clinical trial for acute lymphoblastic leukemia. Here we characterize the death mechanism activated by everolimus in acute lymphoblastic leukemia cells. We find that cell death is caspase-independent and lacks the morphology associated with apoptosis. Althou

SUBMITTER: Baraz R 

PROVIDER: S-EPMC4094511 | biostudies-literature | 2014

REPOSITORIES: biostudies-literature