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
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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