PNP inhibitors selectively kill cancer cells lacking SAMHD1

Purine nucleoside phosphorylase inhibitors (PNP-Is) were developed to ablate transformed lymphocytes. However, only some patients with leukemia benefit from PNP-Is. We provide a molecular explanation: the deoxyribonucleoside triphosphate (dNTP) hydrolase SAM and HD domain-containing protein 1 (SAMHD...

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Autores principales: Davenne, Tamara, Rehwinkel, Jan
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Taylor & Francis 2020
Materias:
Author’s Views
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7671039/
https://www.ncbi.nlm.nih.gov/pubmed/33235905
http://dx.doi.org/10.1080/23723556.2020.1804308
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author Davenne, Tamara
Rehwinkel, Jan
author_facet Davenne, Tamara
Rehwinkel, Jan
author_sort Davenne, Tamara
collection PubMed
description Purine nucleoside phosphorylase inhibitors (PNP-Is) were developed to ablate transformed lymphocytes. However, only some patients with leukemia benefit from PNP-Is. We provide a molecular explanation: the deoxyribonucleoside triphosphate (dNTP) hydrolase SAM and HD domain-containing protein 1 (SAMHD1) prevents the accumulation of toxic dNTP levels during purine nucleoside phosphorylase inhibition. We propose PNP-Is for targeted therapy of patients with acquired SAMHD1 mutations.
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spelling pubmed-76710392020-11-23 PNP inhibitors selectively kill cancer cells lacking SAMHD1 Davenne, Tamara Rehwinkel, Jan Mol Cell Oncol Author’s Views Purine nucleoside phosphorylase inhibitors (PNP-Is) were developed to ablate transformed lymphocytes. However, only some patients with leukemia benefit from PNP-Is. We provide a molecular explanation: the deoxyribonucleoside triphosphate (dNTP) hydrolase SAM and HD domain-containing protein 1 (SAMHD1) prevents the accumulation of toxic dNTP levels during purine nucleoside phosphorylase inhibition. We propose PNP-Is for targeted therapy of patients with acquired SAMHD1 mutations. Taylor & Francis 2020-09-20 /pmc/articles/PMC7671039/ /pubmed/33235905 http://dx.doi.org/10.1080/23723556.2020.1804308 Text en © 2020 The Author(s). Published with license by Taylor & Francis Group, LLC. https://creativecommons.org/licenses/by-nc-nd/4.0/This is an Open Access article distributed under the terms of the Creative Commons Attribution-NonCommercial-NoDerivatives License (http://creativecommons.org/licenses/by-nc-nd/4.0/ (https://creativecommons.org/licenses/by-nc-nd/4.0/) ), which permits non-commercial re-use, distribution, and reproduction in any medium, provided the original work is properly cited, and is not altered, transformed, or built upon in any way.
spellingShingle Author’s Views
Davenne, Tamara
Rehwinkel, Jan
PNP inhibitors selectively kill cancer cells lacking SAMHD1
title PNP inhibitors selectively kill cancer cells lacking SAMHD1
title_full PNP inhibitors selectively kill cancer cells lacking SAMHD1
title_fullStr PNP inhibitors selectively kill cancer cells lacking SAMHD1
title_full_unstemmed PNP inhibitors selectively kill cancer cells lacking SAMHD1
title_short PNP inhibitors selectively kill cancer cells lacking SAMHD1
title_sort pnp inhibitors selectively kill cancer cells lacking samhd1
topic Author’s Views
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7671039/
https://www.ncbi.nlm.nih.gov/pubmed/33235905
http://dx.doi.org/10.1080/23723556.2020.1804308
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AT rehwinkeljan pnpinhibitorsselectivelykillcancercellslackingsamhd1

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