Host thiopurine methyltransferase status affects mercaptopurine antileukemic effectiveness in a murine model
نویسندگان
چکیده
منابع مشابه
Host thiopurine methyltransferase status affects mercaptopurine antileukemic effectiveness in a murine model.
BACKGROUND Thiopurines 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 METHODS We treated thiopurine-sensitive BCR-ABL+Arf-null Tpmt+/+ AL...
متن کاملMolecular dynamics simulation of a human thiopurine S-methyltransferase complexed with 6-mercaptopurine model
Human thiopurine S-methyltransferase (TPMT) is an essential protein in 6-mercaptopurine (6MP) drug metabolism. To understand the pharmacogenetics of TPMT and 6MP, X-ray co-crystal structures of TPMT complexes with S-adenosyl-L-methionine (AdoMet) and 6MP are required. However, the co-crystal structure of this complex has not been reported because 6MP is poorly water soluble. We used molecular d...
متن کاملA cost effectiveness analysis of thiopurine methyltransferase testing for guiding 6-mercaptopurine dosing in children with acute lymphoblastic leukemia.
BACKGROUND An increased understanding of the genetic basis of disease creates a demand for personalized medicine and more genetic testing for diagnosis and treatment. The objective was to assess the incremental cost-effectiveness per life-month gained of thiopurine methyltransferase (TPMT) genotyping to guide doses of 6-mercaptopurine (6-MP) in children with acute lymphoblastic leukemia (ALL) c...
متن کاملRelevance of thiopurine methyltransferase status in rheumatology patients receiving azathioprine.
Azathioprine (AZA) is widely used in the management of rheumatological diseases. Despite its efficacy, AZA can often cause bone marrow suppression, notably leucopenia, which has been recorded in up to 17% of patients taking AZA for rheumatoid arthritis, though this can be considered clinically significant in about 3% overall. Severe myelosuppression, associated with abnormal AZA metabolism, is ...
متن کاملDiffering contribution of thiopurine methyltransferase to mercaptopurine versus thioguanine effects in human leukemic cells.
Thioguanine and mercaptopurine are prodrugs requiring conversion into thiopurine nucleotides to exert cytotoxicity. Thiopurine S-methyltransferase (TPMT), an enzyme subject to genetic polymorphism, catabolizes thiopurines into inactive methylated bases, but also produces methylthioguanine nucleotides and methylmercaptopurine nucleotides from thioguanine and mercaptopurine nucleotides, respectiv...
متن کاملذخیره در منابع من
با ذخیره ی این منبع در منابع من، دسترسی به آن را برای استفاده های بعدی آسان تر کنید
ژورنال
عنوان ژورنال: Pharmacogenetics and Genomics
سال: 2014
ISSN: 1744-6872
DOI: 10.1097/fpc.0000000000000044