ArticleCancer research2008
Transporter-mediated protection against thiopurine-induced hematopoietic toxicity.
Article in Cancer research, 2008. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 56 papers.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
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
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.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
56 citing papers in PubMed, 140 citations in OpenAlex.
- Inherited NUDT15 variant is a genetic determinant of mercaptopurine intolerance in children with acute lymphoblastic leukemia.Journal of clinical oncology : official journal of the American Society of Clinical Oncology · 2015Trial
- Thiopurine pharmacogenomics: association of SNPs with clinical response and functional validation of candidate genes.Pharmacogenomics · 2014Trial
- The role of pharmacogenetics in the therapy regimen of acute lymphoblastic leukemia in children: recent discoveries and future perspectives.Pharmacological reports : PR · 2026Review
- Drug Interaction-Informed Approaches to Inflammatory Bowel Disease Management.Pharmaceutics · 2024Review
- Loss-of-function polymorphisms in NQO1 are not associated with the development of subacute myelo-optico-neuropathy.Molecular genetics & genomic medicine · 2024Article
- ABCC4 impacts megakaryopoiesis and protects megakaryocytes against 6-mercaptopurine induced cytotoxicity.Drug resistance updates : reviews and commentaries in antimicrobial and anticancer chemotherapy · 2024Article
- Association between genetic variants of membrane transporters and the risk of high-grade hematologic adverse events in a cohort of Mexican children with B-cell acute lymphoblastic leukemia.Frontiers in oncology · 2023Article
- Founder genetic variants of ABCC4 and ABCC11 in the Japanese population are not associated with the development of subacute myelo-optico-neuropathy (SMON).Molecular genetics & genomic medicine · 2022Article
- Optimizing thiopurine therapy in children with acute lymphoblastic leukemia: A promising "MINT" sequencing strategy and therapeutic "DNA-TG" monitoring.Frontiers in pharmacology · 2022Review
- Article
- Pharmacogenomics with red cells: a model to study protein variants of drug transporter genes.Vox sanguinis · 2021Review
- Article
- Association Between Genetic Polymorphisms of Metabolic Enzymes and Azathioprine-Induced Myelosuppression in 1,419 Chinese Patients: A Retrospective Study.Frontiers in pharmacology · 2021Article
- Precision medicine for rheumatologists: lessons from the pharmacogenomics of azathioprine.Clinical rheumatology · 2021Review
- Combining clinical and candidate gene data into a risk score for azathioprine-associated leukopenia in routine clinical practice.The pharmacogenomics journal · 2020Article
- Diurnal expression of MRP4 in bone marrow cells underlies the dosing-time dependent changes in the oxaliplatin-induced myelotoxicity.Scientific reports · 2020Article
- Using Pharmacology to Squeeze the Life Out of Childhood Leukemia, and Potential Strategies to Achieve Breakthroughs in Medulloblastoma Treatment.Pharmacological reviews · 2020Review
- Article
- Clioquinol: To harm or heal.Pharmacology & therapeutics · 2019Review
- Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
17 authors at 4 institutions in 5 countries.
Funding
Abstract
Thiopurines are effective immunosuppressants and anticancer agents, but intracellular accumulation of their active metabolites (6-thioguanine nucleotides, 6-TGN) causes dose-limiting hematopoietic toxicity. Thiopurine S-methyltransferase deficiency is known to exacerbate thiopurine toxicity. However, many patients are highly sensitive to thiopurines for unknown reasons. We show that multidrug-resistance protein 4 (Mrp4) is abundant in myeloid progenitors and tested the role of the Mrp4, an ATP transporter of monophosphorylated nucleosides, in this unexplained thiopurine sensitivity. Mrp4-deficient mice experienced Mrp4 gene dosage-dependent toxicity caused by accumulation of 6-TGNs in their myelopoietic cells. Therefore, Mrp4 protects against thiopurine-induced hematopoietic toxicity by actively exporting thiopurine nucleotides. We then identified a single-nucleotide polymorphism (SNP) in human MRP4 (rs3765534) that dramatically reduces MRP4 function by impairing its cell membrane localization. This SNP is common (>18%) in the Japanese population and indicates that the increased sensitivity of some Japanese patients to thiopurines may reflect the greater frequency of this MRP4 SNP.
Indexed as
Identifiers
What OpenQuestion holds
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.