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SAMHD1 Limits the Efficacy of Forodesine in Leukemia by Protecting Cells against the Cytotoxicity of dGTP

Davenne, Tamara ; Klintman, Jenny LU ; Sharma, Sushma ; Rigby, Rachel E. ; Blest, Henry T.W. ; Cursi, Chiara ; Bridgeman, Anne ; Dadonaite, Bernadeta ; De Keersmaecker, Kim and Hillmen, Peter , et al. (2020) In Cell Reports 31(6).
Abstract

SAMHD1 degrades deoxyribonucleoside triphosphates (dNTPs), the building blocks of DNA. Davenne et al. find that SAMHD1 protects cells against dNTP imbalances. Exposure of SAMHD1-deficient cells to deoxyguanosine (dG) results in increased intracellular dGTP levels and subsequent apoptosis. This can be exploited to selectively kill cancer cells that acquired SAMHD1 mutations.

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publishing date
type
Contribution to journal
publication status
published
subject
keywords
apoptosis, BCX-1777, chronic lymphocytic leukemia, CyTOF, deoxyguanosine, dGTP, dNTP, forodesine, Immucillin H, SAMHD1
in
Cell Reports
volume
31
issue
6
article number
107640
publisher
Cell Press
external identifiers
  • pmid:32402273
  • scopus:85084344520
ISSN
2211-1247
DOI
10.1016/j.celrep.2020.107640
language
English
LU publication?
no
id
74bec4fe-e0ac-473e-9237-055d9cb8f468
date added to LUP
2020-11-26 14:25:09
date last changed
2024-03-05 14:08:01
@article{74bec4fe-e0ac-473e-9237-055d9cb8f468,
  abstract     = {{<p>SAMHD1 degrades deoxyribonucleoside triphosphates (dNTPs), the building blocks of DNA. Davenne et al. find that SAMHD1 protects cells against dNTP imbalances. Exposure of SAMHD1-deficient cells to deoxyguanosine (dG) results in increased intracellular dGTP levels and subsequent apoptosis. This can be exploited to selectively kill cancer cells that acquired SAMHD1 mutations.</p>}},
  author       = {{Davenne, Tamara and Klintman, Jenny and Sharma, Sushma and Rigby, Rachel E. and Blest, Henry T.W. and Cursi, Chiara and Bridgeman, Anne and Dadonaite, Bernadeta and De Keersmaecker, Kim and Hillmen, Peter and Chabes, Andrei and Schuh, Anna and Rehwinkel, Jan}},
  issn         = {{2211-1247}},
  keywords     = {{apoptosis; BCX-1777; chronic lymphocytic leukemia; CyTOF; deoxyguanosine; dGTP; dNTP; forodesine; Immucillin H; SAMHD1}},
  language     = {{eng}},
  month        = {{05}},
  number       = {{6}},
  publisher    = {{Cell Press}},
  series       = {{Cell Reports}},
  title        = {{SAMHD1 Limits the Efficacy of Forodesine in Leukemia by Protecting Cells against the Cytotoxicity of dGTP}},
  url          = {{http://dx.doi.org/10.1016/j.celrep.2020.107640}},
  doi          = {{10.1016/j.celrep.2020.107640}},
  volume       = {{31}},
  year         = {{2020}},
}