Print page Print page
Switch language
Rigshospitalet - a part of Copenhagen University Hospital

Role of TPMT and ITPA variants in mercaptopurine disposition

Research output: Contribution to journalJournal articleResearchpeer-review

  1. Parenthood among men diagnosed with cancer in childhood and early adulthood: trends over time in a Danish national cohort

    Research output: Contribution to journalJournal articleResearchpeer-review

  2. Play interventions for paediatric patients in hospital: a scoping review

    Research output: Contribution to journalReviewpeer-review

  3. Value of flow cytometry for MRD-based relapse prediction in B-cell precursor ALL in a multicenter setting

    Research output: Contribution to journalJournal articleResearchpeer-review

  4. The Need for Hospitalization due to SARS-CoV-2 in Children: A Population-based Estimate

    Research output: Contribution to journalLetterpeer-review

View graph of relations

PURPOSE: To explore the levels of thioguanine incorporated into DNA (DNA-TG), and erythrocyte levels of 6-thioguanine nucleotides (Ery-TGN) and methylated metabolites (Ery-MeMP) during 6-mercaptopurine (6MP)/Methotrexate (MTX) therapy of childhood acute lymphoblastic leukemia (ALL) and the relation to inosine triphosphatase (ITPA) and thiopurine methyltransferase (TPMT) gene variants.

METHODS: Blood samples were drawn during 6MP/MTX maintenance therapy from 132 children treated for ALL at Rigshospitalet, Copenhagen. The samples were analysed for thiopurine metabolites and compared to TPMT (rs1800460 and rs1142345) and ITPA (rs1127354) genotypes.

RESULTS: Median DNA-TG (mDNA-TG) levels were higher in TPMT and ITPA low-activity patients as compared to wildtype patients (TPMTLA 549 vs. 364 fmol/µg DNA, p = 0.007, ITPALA 465 vs. 387 fmol/µg DNA, p = 0.04). mDNA-TG levels were positively correlated to median Ery-TGN (mEry-TGN)(rs = 0.37, p = 0.001), but plateaued at higher mEry-TGN levels. DNA-TG indices (mDNA-TG/mEry-TGN) were 42% higher in TPMTWT patients as compared to TPMTLA patients but no difference in DNA-TG indices was observed between ITPAWT and ITPALA patients (median 1.7 vs. 1.6 fmol/µg DNA/ nmol/mmol Hb, p = 0.81). DNA-TG indices increased with median Ery-MeMP (mEry-MeMP) levels (rs = 0.25, p = 0.001).

CONCLUSIONS: TPMT and ITPA genotypes significantly influence the metabolism of 6MP. DNA-TG may prove to be a more relevant pharmacokinetic parameter for monitoring 6MP treatment intensity than cytosolic metabolites. Prospective trials are needed to evaluate the usefulness of DNA-TGN for individual dose adjustments in childhood ALL maintenance therapy.

Original languageEnglish
JournalCancer Chemotherapy and Pharmacology
Issue number3
Pages (from-to)579-586
Number of pages8
Publication statusPublished - Mar 2018

ID: 56423087