{"doi":"10.1111/cts.12861","title":"DNA Methylation‐Based Epigenetic Repression of <i>SLC22A4</i> Promotes Resistance to Cytarabine in Acute Myeloid Leukemia","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.","journal":"Clinical and Translational Science","year":2020,"id":64720,"datarank":0.0,"base_score":0.0,"endowment":0.0,"self_citation_contribution":0.0,"citation_network_contribution":0.0,"self_endowment_contribution":0.0,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":26,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.944,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2020-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":343336,"name":"Jason T. Anderson","orcid":null,"position":1,"is_corresponding":false},{"id":254765,"name":"Stanley Pounds","orcid":"0000-0002-9167-2114","position":2,"is_corresponding":false},{"id":258238,"name":"Lei Shi","orcid":"0000-0002-5312-8521","position":3,"is_corresponding":false},{"id":342106,"name":"Jatinder K. Lamba","orcid":"0000-0003-0411-0007","position":4,"is_corresponding":false},{"id":255307,"name":"Shuiying Hu","orcid":"0000-0002-9806-7734","position":5,"is_corresponding":false},{"id":310490,"name":"Alice A. Gibson","orcid":"0000-0001-5910-5067","position":6,"is_corresponding":false},{"id":343337,"name":"Emily A. Goodwin","orcid":null,"position":7,"is_corresponding":false},{"id":255308,"name":"Alex Sparreboom","orcid":"0000-0003-2660-6644","position":8,"is_corresponding":false},{"id":342107,"name":"Sharyn D. Baker","orcid":"0000-0003-3062-3252","position":9,"is_corresponding":false},{"id":342105,"name":"Daelynn R. Buelow","orcid":"0000-0002-4413-5711","position":0,"is_corresponding":true}],"reference_count":30,"raw_metadata":null,"created_at":"2026-07-18T21:12:58.081635Z","pmid":"32905646","pmcid":null,"fwci":null,"citation_percentile":null,"influential_citations":0,"oa_status":null,"license":null,"views":0,"total_file_size_bytes":0,"version_count":0,"fair_f":null,"fair_a":null,"fair_i":null,"fair_r":null,"fair_zscore":null,"fair_rationale":null,"fair_model":null,"fair_agent_version":null,"fair_fulltext_source":null,"fair_has_llm":null,"fair_computed_at":null,"clinical_trials":[],"software_tools":[],"db_accessions":[],"linked_datasets":[],"topics":[]}