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Oncotarget. 2018 May 22;9(39):25458-25473. doi: 10.18632/oncotarget.25238. eCollection 2018 May 22.

STK3 is a therapeutic target for a subset of acute myeloid leukemias.

Author information

1
Universitäts KrebsCentrums Dresden, Medical Systems Biology, Medical Faculty, Technische Universität Dresden, Dresden, Germany.
2
The Novo Nordisk Foundation Center for Protein Research, University of Copenhagen, Copenhagen, Denmark.
3
Department of Internal Medicine I, Medical Faculty, Technische Universität Dresden, Dresden, Germany.
4
Early Clinical Trial Unit, Medical Faculty, Technische Universität Dresden, Dresden, Germany.
5
Current address: Heinrich Pette Institute, Leibniz Institute for Experimental Virology, Hamburg, Germany.
6
German Cancer Research Center (DKFZ), Heidelberg and German Cancer Consortium (DKTK) Partner Site, Dresden, Germany.
7
Department of Pharmaceutical Chemistry, University of Frankfurt, Frankfurt, Germany.
8
Max Planck Institute of Molecular Cell Biology and Genetics, Dresden, Germany.
9
National Center for Tumor Diseases (NCT), University Hospital Carl Gustav Carus, Technische Universität Dresden, Dresden, Germany.

Abstract

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.

KEYWORDS:

AML; STK3; UCN-01; mitosis; personalized medicine

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