With me or against me: Tumor suppressor and drug resistance activities of SAMHD1

Experimental Hematology
Nikolas HeroldTorsten Schaller

Abstract

Sterile alpha motif and histidine/aspartic acid domain-containing protein 1 (SAMHD1) is a (deoxy)guanosine triphosphate (dGTP/GTP)-activated deoxyribonucleoside triphosphate (dNTP) triphosphohydrolase involved in cellular dNTP homoeostasis. Mutations in SAMHD1 have been associated with the hyperinflammatory disease Aicardi-Goutières syndrome (AGS). SAMHD1 also limits cells' permissiveness to infection with diverse viruses, including human immunodeficiency virus (HIV-1), and controls endogenous retroviruses. Increasing evidence supports the role of SAMHD1 as a tumor suppressor. However, SAMHD1 also can act as a resistance factor to nucleoside-based chemotherapies by hydrolyzing their active triphosphate metabolites, thereby reducing response of various malignancies to these anticancer drugs. Hence, informed cancer therapies must take into account the ambiguous properties of SAMHD1 as both an inhibitor of uncontrolled proliferation and a resistance factor limiting the efficacy of anticancer treatments. Here, we provide evidence that SAMHD1 is a double-edged sword for patients with acute myelogenous leukemia (AML). Our time-dependent analyses of The Cancer Genome Atlas (TCGA) AML cohort indicate that high expression of SAMHD1, eve...Continue Reading

Citations

Mar 28, 2018·Autoimmunity·Christopher H Mauney, Thomas Hollis
Jul 9, 2020·International Journal of Cancer. Journal International Du Cancer·Tobias RoiderSascha Dietrich
Sep 29, 2020·Frontiers in Oncology·Toshihide NishimuraHisashi Saji
Jun 3, 2021·International Journal of Molecular Sciences·Guadalupe Rosario Fajardo-OrduñaEdelmiro Santiago-Osorio
Sep 5, 2021·Journal of Molecular Medicine : Official Organ of the Gesellschaft Deutscher Naturforscher Und Ärzte·Kerstin SchottRenate König
Nov 6, 2021·Virchows Archiv : an International Journal of Pathology·Magali MerrienBirgitta Sander
Jul 10, 2019·Acta Haematologica·Torsten Schaller, Nikolas Herold

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