ArticleCell reports2020
SAMHD1 Limits the Efficacy of Forodesine in Leukemia by Protecting Cells against the Cytotoxicity of dGTP.
Article in Cell reports, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 17 papers.
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Who cites it
17 citing papers in PubMed, 23 citations in OpenAlex.
- Adenosine signaling promotes double-negative T-cell anticancer responses in conditions of CD8 T-cell lymphopenia.Blood immunology & cellular therapy · 2026Article
- IMPDH inhibition enhances cytarabine efficacy in SAMHD1-expressing leukaemia cells via guanine nucleotide depletion.Molecular oncology · 2026Article
- Continuous assay for the dNTP triphosphohydrolase of activated SAMHD1.Analytical biochemistry · 2026Article
- Transition State Analysis of SAMHD1 from PrimaryJournal of the American Chemical Society · 2025Article
- Landscape of targets within nucleoside metabolism for the modification of immune responses.Frontiers in oncology · 2025Review
- Understanding the interplay between dNTP metabolism and genome stability in cancer.Disease models & mechanisms · 2024Review
- Removal of innate immune barriers allows efficient transduction of quiescent human hematopoietic stem cells.Molecular therapy : the journal of the American Society of Gene Therapy · 2024Article
- Discovery of a novel nucleoside immune signaling molecule 2'-deoxyguanosine in microbes and plants.Journal of advanced research · 2023Article
- Deficiency for SAMHD1 activates MDA5 in a cGAS/STING-dependent manner.The Journal of experimental medicine · 2023Article
- Targeting the DNA damage response and repair in cancer through nucleotide metabolism.Molecular oncology · 2022Review
- Purine nucleoside phosphorylase enables dual metabolic checkpoints that prevent T cell immunodeficiency and TLR7-associated autoimmunity.The Journal of clinical investigation · 2022Article
- Nucleotide imbalance decouples cell growth from cell proliferation.Nature cell biology · 2022Article
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- Guanosine primes acute myeloid leukemia for differentiation via guanine nucleotide salvage synthesis.American journal of cancer research · 2022Article
- PNP inhibitors selectively kill cancer cells lacking SAMHD1.Molecular & cellular oncology · 2020Article
Corrections and comments
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Authors and funding
13 authors at 4 institutions in 3 countries.
Funding
Abstract
The anti-leukemia agent forodesine causes cytotoxic overload of intracellular deoxyguanosine triphosphate (dGTP) but is efficacious only in a subset of patients. We report that SAMHD1, a phosphohydrolase degrading deoxyribonucleoside triphosphate (dNTP), protects cells against the effects of dNTP imbalances. SAMHD1-deficient cells induce intrinsic apoptosis upon provision of deoxyribonucleosides, particularly deoxyguanosine (dG). Moreover, dG and forodesine act synergistically to kill cells lacking SAMHD1. Using mass cytometry, we find that these compounds kill SAMHD1-deficient malignant cells in patients with chronic lymphocytic leukemia (CLL). Normal cells and CLL cells from patients without SAMHD1 mutation are unaffected. We therefore propose to use forodesine as a precision medicine for leukemia, stratifying patients by SAMHD1 genotype or expression.
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