Effects on transmethylation by high-dose 6-mercaptopurine and methotrexate infusions during consolidation treatment of acute lymphoblastic leukemia.

  title={Effects on transmethylation by high-dose 6-mercaptopurine and methotrexate infusions during consolidation treatment of acute lymphoblastic leukemia.},
  author={C. W. Keuzenkamp-Jansen and R. D. De Abreu and H. Blom and J. B{\"o}kkerink and J. Trijbels},
  journal={Biochemical pharmacology},
  volume={51 9},
6-mercaptopurine (6MP) cytotoxicity is caused by thioguanine and methylthioinosine nucleotides. Thiopurine methylation occurs to a large extent in vivo and in vitro. In this reaction, S-adenosyl-L-methionine (AdoMet), produced from methionine and ATP, is converted into S-adenosyl-L-homocysteine (AdoHcy) which, in turn, is hydrolyzed into homocysteine. Remethylation of homocysteine into methionine is inhibited by methotrexate (MTX). In cultured lymphoblasts, AdoMet: AdoHcy ratio and DNA… Expand
7 Citations
Demyelination and single-carbon transfer pathway metabolites during the treatment of acute lymphoblastic leukemia: CSF studies.
Treatment of ALL causes marked abnormalities in the single-carbon transfer pathway and subclinical demyelination and whether these abnormalities contribute to the late cognitive deficits requires further study. Expand
Rational administration schedule for high-dose methotrexate in patients with primary central nervous system lymphoma
The impact of patient, lymphoma and pharmacokinetic variables on the antitumor activity of high-dose MTX in patients with PCNSL is analyzed, recommendations for daily clinical practice are summarized and some suggestions for future trials are given. Expand
In vitro study of 6-mercaptopurine oxidation catalysed by aldehyde oxidase and xanthine oxidase.
According to the results obtained from the inhibition studies, it is more likely that 6- mercaptopurine is oxidized to 6-thiouric acid via6-thioxanthine rather than 8-oxo-6-mercaptopurine. Expand
Molecular diagnosis of hereditary thrombotic disorders.
Homocysteine metabolism is influenced by the use of alcohol, anticonvulsant drugs, cyclosporine, methotrexate, inadequate dietary vitamin B, folate and pyridoxine intake, organ transplantation, and reduced creatinine clearance. Expand
Voltammetric determination of 6-mercaptopurine using [Co(phen)3]3+/MWNT modified graphite electrode
Abstract [Co(phen) 3 ] 3+ /multi-walled carbon nanotubes modified graphite electrode ([Co(phen) 3 ] 3+ /MWNT/C) has been developed to monitor quantitatively 6-mercaptopurine (6-MP) concentration andExpand
CTAB functionalized multiwalled carbon nanotube composite modified electrode for the determination of 6-mercaptopurine
Abstract In this work the electrochemical behavior of 6-mercaptopurine (6-MP) on MWCNT-CTAB modified glassy carbon electrode (GCE) is reported in a phosphate buffer solution, pH 3.0. CyclicExpand
Boron carbon oxyphosphide heterostructured nanodots with phosphate tunable emission for switchable dual detection channels of 6-mercaptopurine assay.
This study proposed a novel boron-carbon-phosphorus-oxygen (BCPO) nanodot with phosphate tunable near-ultraviolet emission performance and narrow full width at half maximum by a facile, green and gentle synthesis process to inspire the in-depth application of the BCPO and other nanomaterial-based probes. Expand


Acute and long-term effects of high-dose methotrexate treatment on homocysteine in plasma and urine.
It is suggested that the homocysteine response is not caused by an imbalance in methionine metabolism due to malignant disease or chemotherapy, and that the amount of homocy steine in plasma and urine decreased as a function of the number of MTX infusions. Expand
Decrease in S-adenosylmethionine synthesis by 6-mercaptopurine and methylmercaptopurine ribonucleoside in Molt F4 human malignant lymphoblasts.
Both drugs cause a decrease in intracellular S-Ado-Met concentrations and an increase in S- adenosylhomocysteine and methionine concentrations in Molt F4 human malignant lymphoblasts, and may be an additional mechanism of cytotoxicity for 6-MP and Me-MPR. Expand
6-Mercaptopurine: cytotoxicity and biochemical pharmacology in human malignant T-lymphoblasts.
The data suggest that inhibition of PDNS due to Me-tIMP is a crucial event in the mechanism of 6MP cytotoxicity, responsible for decreased RNA synthesis and decreased availability of natural deoxyribonucleotides, causing a delay of DNA synthesis in S phase. Expand
A biochemical basis for synergism of 6-mercaptopurine and mycophenolic acid in Molt F4, a human malignant T-lymphoblastic cell line.
It is concluded that methylation of tIMP into Me-tIMP is an important alternative route for 6MP cytotoxicity. Expand
Changes in plasma methionine and total homocysteine levels in patients receiving methotrexate infusions.
Investigation of the effects of moderate dose to very high dose methotrexate on methionine and total homocysteine as reflections of metotrexate induced intracellular events found changes in homocy steine and methionines may reflect biological effects of methot Rexate that may predict cytotoxicity of metHotrexate. Expand
Congenital thiopurine methyltransferase deficiency and 6-mercaptopurine toxicity during treatment for acute lymphoblastic leukaemia.
Two children with acute lymphoblastic leukaemia (ALL) taking daily 6-mercaptopurine as part of a national UK therapeutic trial repeatedly developed profound myelosuppression on 25% of the standardExpand
Determination of extracellular and intracellular thiopurines and methylthiopurines by high-performance liquid chromatography.
The thiopurine antimetabolites 6-thioguanine and 6-mercaptopurine are important chemotherapeutic drugs in the treatment of childhood acute lymphoblasts and peripheral mononuclear cells and for methylthioinosine nucleotides in red blood cells. Expand
Polymorphic thiopurine methyltransferase in erythrocytes is indicative of activity in leukemic blasts from children with acute lymphoblastic leukemia.
Examination of variability and relationship of TPMT activity in erythrocytes and lymphoblasts from children with acute lymphoblastic leukemia establishes a new mechanism by which ery Throcytes serve as prognostic markers of mercaptopurine metabolism and TPMM activity in children with ALL. Expand
Thiopurine induced disturbance of DNA methylation in human malignant cells.
The studies described indicate that me-t-IMP formation is an important pathway, contributing to cytotoxicity in Molt F4 cells, which exhibit a highly active de novo purine synthesis. On three levelsExpand
Purine substrates for human thiopurine methyltransferase.
Thiopurine methyltransferase (TPMT) catalyzes the S-methylation of thiopurine drugs such as 6-mercaptopurine (6-MP) and 6-thioguanine (6-TG). A genetic polymorphism regulating TPMT activity in humanExpand