Therapeutic targeting of Aurora A kinase in Philadelphia chromosome-positive ABL tyrosine kinase inhibitor-resistant cells.

ABSTRACT: Abelson murine leukemia viral oncogene homolog (ABL) tyrosine kinase inhibitors (TKIs) have been shown to be effective for treatment of chronic myeloid leukemia (CML) and Philadelphia chromosome-positive (Ph+) acute lymphoblastic leukemia patients. However, resistance to ABL TKIs can develop as a result of breakpoint cluster region-ABL point mutations. Aurora kinases regulate many processes associated with mitosis. In this study, we investigated whether inhibiting Aurora kinase can reduce the viability of Ph+ leukemia cells. Treatment with the Aurora kinase A inhibitor alisertib blocked Ph+ leukemia cell proliferation and Aurora kinase A phosphorylation; it also induced G2/M-phase arrest and increased the intracellular levels of reactive oxygen species. Combined treatment of Ph+ cells with

SUBMITTER: Okabe S 

PROVIDER: S-EPMC6126699 | biostudies-literature | 2018 Aug

REPOSITORIES: biostudies-literature