Thiopurine methyltransferase in acute lymphoblastic leukaemia: Biochemical and molecular biological aspects

Connie Brouwer, Ronney A. De Abreu, Jenneke J. Keizer-Garritsen, Lambert H.J. Lambooy, Kai Ament, Patricia G.J.H. Ter Riet, Elisabeth R. Van Wering, Frans J.M. Trijbels, Anjo J.P. Veerman, Peter M. Hoogerbrugge, Jos P.M. Bökkerink

Onderzoeksoutput: Bijdrage aan tijdschriftArtikelpeer review

42 Citaten (Scopus)


Thiopurine S-methyltransferase (TPMT) is a cytosolic enzyme, catalysing S-methylation of aromatic and heterocyclic sulphhydryl compounds. TPMT activities and genotypes have been determined in patients with acute lymphoblastic leukaemia (ALL) and in control children. Median red blood cell (RBC) TPMT activity in ALL patients at diagnosis was significantly lower than in controls (median 11.5 pmol/107 RBC*hr; range 1.7-30.7; n = 191 vs. 14.6 pmol/107 RBC*hr; range 1.6-50.7; n = 140). This reduction of TPMT activity in ALL patients was not due to differences in the frequency of mutations in the TPMT gene. In concordance with other authors, we found a higher TPMT activity during maintenance treatment with 6-mercaptopurine (6MP) than at diagnosis and in controls. However, we observed that TPMT activity was already significantly increased after the induction therapy, before the patients received 6MP (median 17.5; range 3.9-40.3 pmol/107 RBC*hr; n = 139). In vitro experiments indicate that the early increase of TPMT activity during treatment may be explained by the use of antifolates, e.g., methotrexate and trimethoprim.

Originele taal-2Engels
Pagina's (van-tot)613-623
Aantal pagina's11
TijdschriftEuropean Journal of Cancer
Nummer van het tijdschrift4
StatusGepubliceerd - mrt. 2005
Extern gepubliceerdJa


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