ArticlePharmacogenetics and genomics2014
Host thiopurine methyltransferase status affects mercaptopurine antileukemic effectiveness in a murine model.
Article in Pharmacogenetics and genomics, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 10 papers.
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Who cites it
10 citing papers in PubMed, 10 citations in OpenAlex.
- Trial
- Review
- Additive effects of TPMT and NUDT15 on thiopurine toxicity in children with acute lymphoblastic leukemia across multiethnic populations.Journal of the National Cancer Institute · 2024Article
- Dasatinib does not exacerbate dexamethasone-induced osteonecrosis in murine models of acute lymphoblastic leukemia therapy.Pediatric blood & cancer · 2022Article
- Fenofibrate reduces osteonecrosis without affecting antileukemic efficacy in dexamethasone-treated mice.Haematologica · 2021Article
- Association between theGenes · 2020Article
- Pharmacogenomics and ALL treatment: How to optimize therapy.Seminars in hematology · 2020Review
- Article
- Thiopurine S-methyltransferase activity in Nigerians: phenotypes and activity reference values.BMC research notes · 2018Article
- Antileukemic Efficacy of Continuous vs Discontinuous Dexamethasone in Murine Models of Acute Lymphoblastic Leukemia.PloS one · 2015Article
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Authors and funding
8 authors at 4 institutions in 1 country.
Funding
Abstract
backgroundThiopurines are used for many cancers, including acute lymphoblastic leukemia (ALL). Patients with an inherited host defect in thiopurine methyltransferase (TPMT) are at high risk for life-threatening toxicity if treated with conventional dosages, but the impact on antileukemic efficacy is less clear. MATERIALS AND
methodsWe treated thiopurine-sensitive BCR-ABL+Arf-null Tpmt+/+ ALL in Tpmt+/+, +/-, or -/- recipient mice to test the impact of the host polymorphism on antileukemic efficacy.
resultsMedian survival was similar in untreated mice of different Tpmt genotypes (16-18 days). However, in mice treated with low-dose mercaptopurine (such as tolerated by TPMT-/- patients), the difference in 30-day leukemia-free survival by Tpmt genotype was profound: 5% (±9%) for Tpmt+/+ mice, 47% (±26%) for Tpmt+/- mice, and 85% (±14%) for Tpmt-/- mice (P=5×10), indicating a substantial impact of host Tpmt status on thiopurine effectiveness. Among Tpmt+/+ recipient mice, leukemia-free survival improved with higher doses of mercaptopurine (similar to doses tolerated by wild-type patients) compared with lower doses, and at higher doses was comparable (P=0.6) to the survival of Tpmt-/- mice treated with the lower dose.
conclusionsThese findings support the notion that germline polymorphisms in Tpmt affect not only host tissue toxicity but also antitumor effectiveness.
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