ArticleClinical and translational science2021
DNA Methylation-Based Epigenetic Repression of SLC22A4 Promotes Resistance to Cytarabine in Acute Myeloid Leukemia.
Article in Clinical and translational science, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 17 papers.
What it found
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Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
17 citing papers in PubMed, 24 citations in OpenAlex.
- Organic cation transporter novel 1 (OCTN1): beyond an ergothioneine transporter.Cell communication and signaling : CCS · 2026Review
- Role of solute carrier transporters in the biodistribution and toxicity of chemotherapeutic drugs.Pharmacological reviews · 2026Review
- Cellular pharmacology of fludarabine: molecular determinants of transport and metabolism.Frontiers in pharmacology · 2026Review
- Construction and Validation of an N7-Methylguanosine-Related Prognostic Model for Acute Myeloid Leukemia.Blood and lymphatic cancer : targets and therapy · 2026Article
- Role of SLC Transporters and Noncoding RNA in Regulating the Genetic Landscape of the Blood Disorders.Experientia supplementum (2012) · 2026Review
- The role of SLC22A4 in Acute Myeloid Leukaemia.Mediterranean journal of hematology and infectious diseases · 2025Article
- Inflammation and Organic Cation Transporters Novel (OCTNs).Biomolecules · 2024Review
- Bone Marrow Microenvironment-Induced Chemoprotection inCancers · 2023Article
- Prognostic value of neutrophil extracellular trap signature in clear cell renal cell carcinoma.Frontiers in oncology · 2023Article
- Targeted Epigenetic Interventions in Cancer with an Emphasis on Pediatric Malignancies.Biomolecules · 2022Review
- Does Intracellular Metabolism Render Gemcitabine Uptake Undetectable in Mass Spectrometry?International journal of molecular sciences · 2022Article
- OCTN1: A Widely Studied but Still Enigmatic Organic Cation Transporter Linked to Human Pathology and Drug Interactions.International journal of molecular sciences · 2022Review
- Feature Genes in Neuroblastoma Distinguishing High-Risk and Non-high-Risk Neuroblastoma Patients: Development and Validation Combining Random Forest With Artificial Neural Network.Frontiers in medicine · 2022Article
- Article
- Hypomethylating Chemotherapeutic Agents as Therapy for Myelodysplastic Syndromes and Prevention of Acute Myeloid Leukemia.Pharmaceuticals (Basel, Switzerland) · 2021Review
- Association of expression of epigenetic molecular factors with DNA methylation and sensitivity to chemotherapeutic agents in cancer cell lines.Clinical epigenetics · 2021Article
- Narrative review of targetable features of pediatric acute myeloid leukemia from molecular and metabolic perspectives.Pediatric medicine (Hong Kong, China) · 2021Article
Corrections and comments
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Authors and funding
10 authors at 3 institutions in 1 country.
Funding
Abstract
Reduced expression of the uptake transporter, OCTN1 (SLC22A4), has been reported as a strong predictor of poor event-free and overall survival in multiple cohorts of patients with acute myeloid leukemia (AML) receiving the cytidine nucleoside analog, cytarabine (Ara-C). To further understand the mechanistic basis of interindividual variability in the functional expression of OCTN1 in AML, we hypothesized a mechanistic connection to DNA methylation-based epigenetic repression of SLC22A4. We found increased basal SLC22A4 methylation was associated with decreased Ara-C uptake in AML cell lines. Pre-treatment with hypomethylating agents, 5-azacytidine, or decitabine, restored SLC22A4 mRNA expression, increased cellular uptake of Ara-C, and was associated with increased cellular sensitivity to Ara-C compared with vehicle-treated cells. Additionally, lower SLC22A4 methylation status was associated with distinct clinical advantages in both adult and pediatric patients with AML. These findings suggest a regulatory mechanism is involved in the interindividual variability in response to Ara-C, and provides a basis for the integration of hypomethylating agents into Ara-C-based treatment regimens.
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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.