CD34+/CD38- acute myelogenous leukemia cells aberrantly express Aurora kinase A

Abstract

We previously showed that Aurora kinase A (AURKA) is aberrantly expressed in acute myelogenous leukemia (AML) cells when compared to bone marrow mononuclear cells isolated from healthy volunteers. We have also shown that CD34+/CD38- AML cells, one of compartments enriched for leukemia stem cells in most leukemia subgroups, were relatively resistant to cytarabine-mediated growth inhibition when compared to their CD34 +/CD38+ counterparts. Our study attempted to identify therapeutic targets in CD34+/CD38- AML cells and found that CD34+/CD38- AML cells isolated from patients (n = 26) expressed larger amounts of AURKA than their CD34+/CD38+ counterparts and CD34+ normal hematopoietic stem/progenitor cells isolated from healthy volunteers (n = 6), as measured by real-time reverse-transcriptase polymerase chain reaction. Blockade of AURKA by the specific inhibitor MLN8237 or a short hairpin RNA (shRNA) against AURKA significantly inhibited proliferation, impaired self-renewal capability and induced apoptosis of CD34+/CD38- AML cells, in association with modulation of levels of Bcl-2 family member proteins. Importantly, inhibition of AURKA in CD34+/CD38- AML cells by MLN8237 or an shRNA significantly impaired engraftment of these cells in severely immunocompromised mice and appeared to prolong their survival. These results suggest that AURKA is a promising molecular target to eliminate chemotherapy-resistant CD34+/CD38- AML cells. Copyright © 2013 UICC.