ArticleLeukemia2018
AZA-MS: a novel multiparameter mass spectrometry method to determine the intracellular dynamics of azacitidine therapy in vivo.
Article in Leukemia, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 13 papers.
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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.
The trial behind it
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Who cites it
13 citing papers in PubMed, 34 citations in OpenAlex.
- Clinical response to azacitidine in MDS is associated with distinct DNA methylation changes in HSPCs.Nature communications · 2025Trial
- RIG-I-Inducing Small Molecules Potently Inhibit HMA-Resistant AML Through Igniting the Overloaded dsRNA Arsenal.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2025Article
- TOPORS E3 ligase mediates resistance to hypomethylating agent cytotoxicity in acute myeloid leukemia cells.Nature communications · 2024Article
- DNA methyltransferase inhibitor exposure-response: Challenges and opportunities.Clinical and translational science · 2023Review
- Solute Carrier Family 29A1 Mediates In Vitro Resistance to Azacitidine in Acute Myeloid Leukemia Cell Lines.International journal of molecular sciences · 2023Article
- Review
- Modulation of IL-6/STAT3 signaling axis in CD4+FOXP3- T cells represents a potential antitumor mechanism of azacitidine.Blood advances · 2021Article
- Resistance to Hypomethylating Agents in Myelodysplastic Syndrome and Acute Myeloid Leukemia From Clinical Data and Molecular Mechanism.Frontiers in oncology · 2021Review
- Induction of muscle-regenerative multipotent stem cells from human adipocytes by PDGF-AB and 5-azacytidine.Science advances · 2021Article
- Intracellular Pharmacokinetics of Pyrimidine Analogues used in Oncology and the Correlation with Drug Action.Clinical pharmacokinetics · 2020Review
- Unravelling the Epigenome of Myelodysplastic Syndrome: Diagnosis, Prognosis, and Response to Therapy.Cancers · 2020Review
- Selective inactivation of hypomethylating agents by SAMHD1 provides a rationale for therapeutic stratification in AML.Nature communications · 2019Article
- Clinical update on hypomethylating agents.International journal of hematology · 2019Review
Corrections and comments
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Authors and funding
8 authors at 3 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
The cytidine analogue, 5-azacytidine (AZA; 5-AZA-cR), is the primary treatment for myelodysplastic syndrome and chronic myelomonocytic leukaemia. However, only ~50% of treated patients will respond to AZA and the drivers of AZA resistance in vivo are poorly understood. To better understand the intracellular dynamics of AZA upon therapy and decipher the molecular basis for AZA resistance, we have developed a novel, multiparameter, quantitative mass spectrometry method (AZA-MS). Using AZA-MS, we have accurately quantified the abundance of the ribonucleoside (5-AZA-cR) and deoxyribonucleoside (5-AZA-CdR) forms of AZA in RNA, DNA and the cytoplasm within the same sample using nanogram quantities of input material. We report that although AZA induces DNA demethylation in a dose-dependent manner, it has no corresponding effect on RNA methylation. By applying AZA-MS to primary bone marrow samples from patients undergoing AZA therapy, we have identified that responders accumulate more 5-AZA-CdR in their DNA compared with nonresponders. AZA resistance was not a result of impaired AZA metabolism or intracellular accumulation. Furthermore, AZA-MS has helped to uncover different modes of AZA resistance. Whereas some nonresponders fail to incorporate sufficient 5-AZA-CdR into DNA, others incorporate 5-AZA-CdR and effect DNA demethylation like AZA responders, but show no clinical benefit.
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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.