Thiopurine methyltransferase: a review and a clinical pilot study
Autor: | Jos P.M. Bökkerink, R.A. de Abreu, P.A.J. Leegwater, C.W. Keuzenkamp-Jansen, M.A.H. Lambooy, J. M. F. Trijbels |
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Rok vydání: | 1996 |
Předmět: |
Biochemische farmacologie van 24-uurs intraveneus methotrexaat
gevolgd door 24-uurs intraveneus hoge-dosis 6-mercaptopurine in protocol SNWLK-ALL-8 voor kinderen met acute lymfatische leuke Antimetabolites Antineoplastic Methyltransferase Stereochemistry medicine.medical_treatment Population Pilot Projects Pharmacology Peripheral blood mononuclear cell Thiopurine S-Methyltransferase Acute lymphocytic leukemia medicine Humans education GeneralLiterature_REFERENCE(e.g. dictionaries encyclopedias glossaries) Chemotherapy education.field_of_study Polymorphism Genetic Chromatography Thiopurine methyltransferase biology Mercaptopurine Chemistry Methyltransferases General Chemistry Precursor Cell Lymphoblastic Leukemia-Lymphoma medicine.disease Inactivation Metabolic biology.protein Biochemical pharmacology of 24-hours intravenous methotrexate followed by 24-hours intravenous high-dose 6-mercaptopurine in protocol SNWLK-ALL-8 for children with acute lymphoblastic leuke medicine.drug |
Zdroj: | Journal of Chromatography. B, 678, Appl, pp. 15-22 Journal of Chromatography. B, 678, 15-22 |
ISSN: | 0378-4347 1570-0232 |
Popis: | Thiopurine methyltransferase (TPMT) is an important enzyme in the metabolism of 6-mercaptopurine (6MP), which is used in the treatment of acute lymphoblastic leukemia (ALL). TPMT catalyzes the formation of methylthioinosine monophosphate (MetIMP), which is cytotoxic for cultured cell lines, and it plays a role in detoxification of 6MP. Population studies show a genetic polymorphism for TPMT with both high and low activity alleles. About 1 of 300 subjects is homozygous for the low activity. The function TPMT plays in detoxification or therapeutic efficacy of 6MP in vivo is not clear. In this article the genetic polymorphism of TPMT is reviewed and the contribution of TPMT to the cytotoxic action, or detoxification, of 6MP in children with ALL is discussed. Induction of TPMT activity has been described during the treatment for ALL. We performed a pilot study on the influence of high-dose 6MP infusions (1300 mg/m2 in 24 h) on TPMT activity of peripheral blood mononuclear cells (pMNC) of eleven patients with ALL. The TPMT activities were in, or, above the normal range. There was no statistically significant difference between the TPMT activities before and after the 6MP infusions. MetIMP levels in pMNC increased during successive courses. This might be explained by TPMT induction, but other explanations are plausible as well. Twenty five percent of the TPMT assays failed, because less than the necessary 5.10(6) pMNC could be isolated from the blood of leukopenic patients. Red blood cells can not be used for TPMT measurements, since transfusions are frequently required during the treatment with 6MP infusions. Therefore, the influence of high-dose 6MP infusions on TPMT activity can only be investigated further when a TPMT assay which requires less pMNC has been developed. |
Databáze: | OpenAIRE |
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