ArticleEMBO molecular medicine2020
Ribonucleotide reductase inhibitors suppress SAMHD1 ara-CTPase activity enhancing cytarabine efficacy.
Article in EMBO molecular medicine, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 45 papers, 1 of them a synthesis that pooled it.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
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Who cites it
45 citing papers in PubMed, 1 synthesis or guideline pooled it, 58 citations in OpenAlex.
- Nelarabine in T-cell acute lymphoblastic leukemia: intracellular metabolism and molecular mode-of-action.Leukemia · 2025Pooled it
- Targeting IMPDH to inhibit SAMHD1 inCell cycle (Georgetown, Tex.) · 2026Article
- Nucleotide Metabolism in Health and Disease.MedComm · 2026Review
- Adaptive Regulation of dNTP Homeostasis Confers Osimertinib Resistance in EGFR-Mutant Non-Small Cell Lung Carcinoma.Cancer research · 2026Article
- Oncogenic DCTPP1/MYC feedback loop rewires pyrimidine metabolism to drive hepatocellular carcinoma.Functional & integrative genomics · 2026Article
- Roles of RRM2 and RRM2B in pyrimidine stress responses and differentiation of acute myeloid leukemia cells.Cell death discovery · 2026Article
- Regulation of ferroptosis in colorectal cancer through therapeutic modulation and miRNA targeting.Biochemistry and biophysics reports · 2026Article
- IMPDH inhibition enhances cytarabine efficacy in SAMHD1-expressing leukaemia cells via guanine nucleotide depletion.Molecular oncology · 2026Article
- Enhancing the Nucleoside Analog Response with Translational Therapeutic Approaches to Overcome Resistance.Cells · 2026Review
- Selective depletion of tumor-associated SAMHD1 enhances chemotherapeutic efficacy and antitumor immune responses.Signal transduction and targeted therapy · 2025Article
- Addition of hydroxyurea (hydroxycarbamide) enhances the efficacy of fludarabine/cytarabine-based salvage regimens against acute myeloid leukaemia.British journal of haematology · 2025Article
- Precision oncology to overcome resistance in R/R AML in children and adults requires combinations of cytotoxic, targeted, and immunological treatments.Journal of internal medicine · 2025Review
- Purine metabolites regulate leukemic cell sensitivity toward cytarabine.Haematologica · 2025Article
- RRM2B deficiency causes dATP and dGTP depletion through enhanced degradation and slower synthesis.Proceedings of the National Academy of Sciences of the United States of America · 2025Article
- SAMHD1 shapes deoxynucleotide triphosphate homeostasis by interconnecting the depletion and biosynthesis of different dNTPs.Nature communications · 2025Article
- Understanding the interplay between dNTP metabolism and genome stability in cancer.Disease models & mechanisms · 2024Review
- Article
- Identification and evaluation of small-molecule inhibitors against the dNTPase SAMHD1 via a comprehensive screening funnel.iScience · 2024Article
- E2F1 rs3213150 polymorphism influences cytarabine sensitivity and prognosis in patients with acute myeloid leukemia.Annals of hematology · 2023Article
- Protein-Targeting Drug Discovery.Biomolecules · 2023Article
Corrections and comments
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Authors and funding
35 authors at 6 institutions in 5 countries.
Funding
Abstract
The deoxycytidine analogue cytarabine (ara-C) remains the backbone treatment of acute myeloid leukaemia (AML) as well as other haematological and lymphoid malignancies, but must be combined with other chemotherapeutics to achieve cure. Yet, the underlying mechanism dictating synergistic efficacy of combination chemotherapy remains largely unknown. The dNTPase SAMHD1, which regulates dNTP homoeostasis antagonistically to ribonucleotide reductase (RNR), limits ara-C efficacy by hydrolysing the active triphosphate metabolite ara-CTP. Here, we report that clinically used inhibitors of RNR, such as gemcitabine and hydroxyurea, overcome the SAMHD1-mediated barrier to ara-C efficacy in primary blasts and mouse models of AML, displaying SAMHD1-dependent synergy with ara-C. We present evidence that this is mediated by dNTP pool imbalances leading to allosteric reduction of SAMHD1 ara-CTPase activity. Thus, SAMHD1 constitutes a novel biomarker for combination therapies of ara-C and RNR inhibitors with immediate consequences for clinical practice to improve treatment of AML.
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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.