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- W2584778529 abstract "Abstract Abstract 1886 Aurora kinase A (AURKA) plays a pivotal role in the mitotic processes during cell division. We previously showed that AURKA was aberrantly expressed in hematological malignant cells including those from acute myelogenous leukemia (AML) and acute lymphoblastic leukemia, compared with CD34+ hematopoietic stem/progenitor cells isolated from healthy volunteers. This study found that freshly isolated CD34+/CD38− cells from individuals with AML (n=12) in which leukemia stem cells were supposed to be enriched expressed a greater amount of AURKA than their CD34+/CD38+ counterparts, as measured by real time RT-PCR. Blockade of AURKA by the specific inhibitor MLN8237 significantly inhibited proliferation and induced apoptosis of CD34+/CD38− AML cells, as assessed by the clonogenic assay and detection of the cleaved form of poly (ADP-ribose) polymerase by Western blot analysis, respectively. In addition, exposure of CD34+/CD38− AML cells to MLN8237 down-regulated levels of Bcl-2 family proteins and increased Bax/Bcl-2 expression ratio. Moreover, inhibition of AURKA by MLN8237 (30mg/kg for 14 consecutive days) impaired engraftment of CD34+/CD38− AML cells in severely immunocompromised mice (n=5, 49±32% in control vs 18±16% in MLN8237 treated mice, P<0.05), and prolonged their overall survival (P<0.05), compared with vehicle treated mice. Taken together, AURKA may be a promising molecular target to eliminate chemotherapy-resistant CD34+/CD38− AML cells. Disclosures: No relevant conflicts of interest to declare." @default.
- W2584778529 created "2017-02-10" @default.
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- W2584778529 date "2011-11-18" @default.
- W2584778529 modified "2023-09-28" @default.
- W2584778529 title "CD34+/CD38− Acute Myelogenous Leukemia Cells Aberrantly Express Aurora Kinase A" @default.
- W2584778529 doi "https://doi.org/10.1182/blood.v118.21.1886.1886" @default.
- W2584778529 hasPublicationYear "2011" @default.
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