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...
| Main Authors: | , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
Taylor & Francis Group
2020-11-01
|
| Series: | Molecular & Cellular Oncology |
| Subjects: | |
| Online Access: | http://dx.doi.org/10.1080/23723556.2020.1804308 |
| _version_ | 1827809344981303296 |
|---|---|
| author | Tamara Davenne Jan Rehwinkel |
| author_facet | Tamara Davenne Jan Rehwinkel |
| author_sort | Tamara Davenne |
| collection | DOAJ |
| 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. |
| first_indexed | 2024-03-11T22:39:55Z |
| format | Article |
| id | doaj.art-729c387c36f747d68bd2d319ab7e7b9c |
| institution | Directory Open Access Journal |
| issn | 2372-3556 |
| language | English |
| last_indexed | 2024-03-11T22:39:55Z |
| publishDate | 2020-11-01 |
| publisher | Taylor & Francis Group |
| record_format | Article |
| series | Molecular & Cellular Oncology |
| spelling | doaj.art-729c387c36f747d68bd2d319ab7e7b9c2023-09-22T09:11:02ZengTaylor & Francis GroupMolecular & Cellular Oncology2372-35562020-11-017610.1080/23723556.2020.18043081804308PNP inhibitors selectively kill cancer cells lacking SAMHD1Tamara Davenne0Jan Rehwinkel1University of OxfordUniversity of OxfordPurine 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.http://dx.doi.org/10.1080/23723556.2020.1804308pnpforodesinesamhd1leukemiacll |
| spellingShingle | Tamara Davenne Jan Rehwinkel PNP inhibitors selectively kill cancer cells lacking SAMHD1 Molecular & Cellular Oncology pnp forodesine samhd1 leukemia cll |
| 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 | pnp forodesine samhd1 leukemia cll |
| url | http://dx.doi.org/10.1080/23723556.2020.1804308 |
| work_keys_str_mv | AT tamaradavenne pnpinhibitorsselectivelykillcancercellslackingsamhd1 AT janrehwinkel pnpinhibitorsselectivelykillcancercellslackingsamhd1 |