STK3 is a therapeutic target for a subset of acute myeloid leukemias
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Aylin Camgoz 1, Maciej Paszkowski-Rogacz1, Shankha Satpathy2, Martin Wermke3,4, Martin V. Hamann1,9, Malte von Bonin3,5, Chunaram Choudhary2, Stefan Knapp6 and Frank Buchholz1,5,7,8
1Universitäts KrebsCentrums Dresden, Medical Systems Biology, Medical Faculty, Technische Universität Dresden, Dresden, Germany
2The Novo Nordisk Foundation Center for Protein Research, University of Copenhagen, Copenhagen, Denmark
3Department of Internal Medicine I, Medical Faculty, Technische Universität Dresden, Dresden, Germany
4Early Clinical Trial Unit, Medical Faculty, Technische Universität Dresden, Dresden, Germany
5German Cancer Research Center (DKFZ), Heidelberg and German Cancer Consortium (DKTK) Partner Site, Dresden, Germany
6Department of Pharmaceutical Chemistry, University of Frankfurt, Frankfurt, Germany
7Max Planck Institute of Molecular Cell Biology and Genetics, Dresden, Germany
8National Center for Tumor Diseases (NCT), University Hospital Carl Gustav Carus, Technische Universität Dresden, Dresden, Germany
9Current address: Heinrich Pette Institute, Leibniz Institute for Experimental Virology, Hamburg, Germany
Frank Buchholz, email: Frank.Buchholz@tu-dresden.de
Keywords: AML; personalized medicine; UCN-01; STK3; mitosis
Received: December 17, 2017 Accepted: April 06, 2018 Published: May 22, 2018
Acute myeloid leukemia (AML) is characterized by uncontrolled proliferation and accumulation of immature myeloblasts, which impair normal hematopoiesis. While this definition categorizes the disease into a distinctive group, the large number of different genetic and epigenetic alterations actually suggests that AML is not a single disease, but a plethora of malignancies. Still, most AML patients are not treated with targeted medication but rather by uniform approaches such as chemotherapy. The identification of novel treatment options likely requires the identification of cancer cell vulnerabilities that take into account the different genetic and epigenetic make-up of the individual tumors. Here we show that STK3 depletion by knock-down, knock-out or chemical inhibition results in apoptotic cells death in some but not all AML cell lines and primary cells tested. This effect is mediated by a premature activation of cyclin dependent kinase 1 (CDK1) in presence of elevated cyclin B1 levels. The anti-leukemic effects seen in both bulk and progenitor AML cells suggests that STK3 might be a promising target in a subset of AML patients.
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