ArticleNature communications2019
Selective inactivation of hypomethylating agents by SAMHD1 provides a rationale for therapeutic stratification in AML.
Article in Nature communications, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 46 papers.
What it found
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Who cites it
46 citing papers in PubMed, 81 citations in OpenAlex.
- Nucleotide Metabolism in Health and Disease.MedComm · 2026Review
- Predicting response to hypomethylating agents in myeloid neoplasms: a robust model.Annals of hematology · 2026Article
- Article
- Targeting Genome Maintenance Defects of Cancers Using Chain-Terminating Nucleoside Analogs.Cancer science · 2026Review
- Allosteric targeting with antiviral nucleotide analogs allows fine-tuning of SAMHD1 dNTPase activity.The Journal of biological chemistry · 2026Article
- RRM1 inhibition sensitizes lung adenocarcinoma to decitabine treatment.Cell death & disease · 2026Article
- Efficacy of azacitidine in meningiomas and explorative analyses of underlying molecular mechanisms.Neurosurgical review · 2026Article
- Article
- Continuous assay for the dNTP triphosphohydrolase of activated SAMHD1.Analytical biochemistry · 2026Article
- Selective depletion of tumor-associated SAMHD1 enhances chemotherapeutic efficacy and antitumor immune responses.Signal transduction and targeted therapy · 2025Article
- Article
- Chromatin Perturbation Promotes Susceptibility to Hypomethylating Agents.bioRxiv : the preprint server for biology · 2025Article
- Advances and challenges in the treatment of myelodysplastic syndromes.Experimental hematology & oncology · 2025Review
- Acquired Resistance to Decitabine Associated with the Deoxycytidine Kinase A180P Mutation: Implications for the Order of Hypomethylating Agents in Myeloid Malignancies Treatment.International journal of molecular sciences · 2025Article
- From Chemotherapy to Targeted Therapy: Unraveling Resistance in Acute Myeloid Leukemia Through Genetic and Non-Genetic Insights.International journal of molecular sciences · 2025Review
- The type of DNA damage response after decitabine treatment depends on the level of DNMT activity.Life science alliance · 2024Article
- Novel Vpx virus-like particles to improve cytarabine treatment response against acute myeloid leukemia.Clinical and experimental medicine · 2024Article
- Decitabine cytotoxicity is promoted by dCMP deaminase DCTD and mitigated by SUMO-dependent E3 ligase TOPORS.The EMBO journal · 2024Article
- Platform-directed allostery and quaternary structure dynamics of SAMHD1 catalysis.Nature communications · 2024Article
- SAMHD1 expression contributes to doxorubicin resistance and predicts survival outcomes in diffuse large B-cell lymphoma patients.NAR cancer · 2024Article
Corrections and comments
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Authors and funding
24 authors at 7 institutions in 4 countries.
Funding
Abstract
Hypomethylating agents decitabine and azacytidine are regarded as interchangeable in the treatment of acute myeloid leukemia (AML). However, their mechanisms of action remain incompletely understood, and predictive biomarkers for HMA efficacy are lacking. Here, we show that the bioactive metabolite decitabine triphosphate, but not azacytidine triphosphate, functions as activator and substrate of the triphosphohydrolase SAMHD1 and is subject to SAMHD1-mediated inactivation. Retrospective immunohistochemical analysis of bone marrow specimens from AML patients at diagnosis revealed that SAMHD1 expression in leukemic cells inversely correlates with clinical response to decitabine, but not to azacytidine. SAMHD1 ablation increases the antileukemic activity of decitabine in AML cell lines, primary leukemic blasts, and xenograft models. AML cells acquire resistance to decitabine partly by SAMHD1 up-regulation. Together, our data suggest that SAMHD1 is a biomarker for the stratified use of hypomethylating agents in AML patients and a potential target for the treatment of decitabine-resistant leukemia.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.