AURKA Suppresses Leukemic THP-1 Cell Differentiation through Inhibition of the KDM6B Pathway
Jin Woo Park1,2, Hana Cho1,2, Hyein Oh1, Ji-Young Kim1,*, and Sang-Beom Seo1,*
1Department of Life Science, College of Natural Sciences, Chung-Ang University, Seoul 156-756, Korea, 2These authors contributed equally to this work.
*Correspondence: (JYK); (SBS)
Received November 22, 2017; Revised January 19, 2018; Accepted February 10, 2018.; Published online February 23, 2018.
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Aberrations in histone modifications are being studied in mixed-lineage leukemia (MLL)-AF9-driven acute myeloid leukemia (AML). In this study, we focused on the regulation of the differentiation of the MLL-AF9 type AML cell line THP-1. We observed that, upon phorbol 12-myristate 13-acetate (PMA) treatment, THP-1 cells differentiated into monocytes by down-regulating Aurora kinase A (AURKA), resulting in a reduction in H3S10 phosphorylation. We revealed that the AURKA inhibitor alisertib accelerates the expression of the H3K27 demethylase KDM6B, thereby dissociating AURKA and YY1 from the KDM6B promoter region. Using Flow cytometry, we found that alisertib induces THP-1 differentiation into monocytes. Furthermore, we found that treatment with the KDM6B inhibitor GSK-J4 perturbed the PMA-mediated differentiation of THP-1 cells. Thus, we discovered the mechanism of AURKA–KDM6B signaling that controls the differentiation of THP-1 cells, which has implications for biotherapy for leukemia.
Keywords: AURKA, differentiation, KDM6B, MLL-AF9 AML, THP-1

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30 April 2018 Volume 41,
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