Thiopurine methyltransferase activity in children with acute myeloid leukemia

  • Authors:
    • Joanna Sobiak
    • Jolanta Skalska‑Sadowska
    • Maria Chrzanowska
    • Matylda Resztak
    • Sylwia Kołtan
    • Mariusz Wysocki
    • Jacek Wachowiak
  • View Affiliations

  • Published online on: July 23, 2018     https://doi.org/10.3892/ol.2018.9191
  • Pages: 4699-4706
Metrics: Total Views: 0 (Spandidos Publications: | PMC Statistics: )
Total PDF Downloads: 0 (Spandidos Publications: | PMC Statistics: )


Abstract

Activity of the enzyme thiopurine methyltransferase (TPMT) determines the anti‑leukemic effect of thiopurines used in the chemotherapy of acute lymphoblastic leukemia (ALL) and acute myeloblastic leukemia (AML). TPMT status and its effects on treatment outcome have been studied extensively in ALL and autoimmune disorders, but few data is available on TPMT in AML. The present study assessed the genetic polymorphisms and activity of TPMT in children with AML at different treatment stages, and compared the results with those obtained for children with ALL. The study included 33 children with AML (0.7‑19.7 years) treated with 6‑thioguanine (6‑TG) according to the AML‑BFM 2004 Protocol. Blood samples were collected at diagnosis, during and following maintenance chemotherapy from 8, 10 and 17 patients with AML (the assay was performed at two time points in 2 patients), respectively. Blood samples from 105 children with ALL were obtained at diagnosis, during the maintenance chemotherapy and following the cessation of the chemotherapy from 16, 55 and 34 children, respectively. The activity of TPMT in red blood cells lysates was measured using an enzymatic reaction based on the conversion of 6‑mercaptopurine into 6‑methylmercaptopurine, involving S‑adenozyl‑L‑methionine as the methyl group donor. TPMT mutations were determined using a polymerase chain reaction/restriction fragment length polymorphism method. Median TPMT activity at diagnosis, during maintenance chemotherapy and following chemotherapy was 43.1, 47,3 and 41.7 nmol 6‑mMP g‑1 Hb h‑1, respectively. All patients with AML exhibited the homozygous TPMT*1/*1 genotype, with the exception of 1, who was a heterozygote with the TPMT*1/*3C genotype and demonstrated a TPMT activity level at diagnosis of 42.5 nmol 6‑mMP g‑1 Hb h‑1. At each chemotherapy stage, the median TPMT activities in children with AML were significantly increased compared with the median TPMT activities in children with ALL. The preliminary results suggest that the TPMT activity in AML may be increased compared with that in ALL. Comprehensive studies on the association between thiopurine metabolism and treatment outcome in AML are required, with regard to the cytogenetic and molecular factors currently used for AML risk stratification.
View Figures
View References

Related Articles

Journal Cover

October-2018
Volume 16 Issue 4

Print ISSN: 1792-1074
Online ISSN:1792-1082

Sign up for eToc alerts

Recommend to Library

Copy and paste a formatted citation
x
Spandidos Publications style
Sobiak J, Skalska‑Sadowska J, Chrzanowska M, Resztak M, Kołtan S, Wysocki M and Wachowiak J: Thiopurine methyltransferase activity in children with acute myeloid leukemia. Oncol Lett 16: 4699-4706, 2018
APA
Sobiak, J., Skalska‑Sadowska, J., Chrzanowska, M., Resztak, M., Kołtan, S., Wysocki, M., & Wachowiak, J. (2018). Thiopurine methyltransferase activity in children with acute myeloid leukemia. Oncology Letters, 16, 4699-4706. https://doi.org/10.3892/ol.2018.9191
MLA
Sobiak, J., Skalska‑Sadowska, J., Chrzanowska, M., Resztak, M., Kołtan, S., Wysocki, M., Wachowiak, J."Thiopurine methyltransferase activity in children with acute myeloid leukemia". Oncology Letters 16.4 (2018): 4699-4706.
Chicago
Sobiak, J., Skalska‑Sadowska, J., Chrzanowska, M., Resztak, M., Kołtan, S., Wysocki, M., Wachowiak, J."Thiopurine methyltransferase activity in children with acute myeloid leukemia". Oncology Letters 16, no. 4 (2018): 4699-4706. https://doi.org/10.3892/ol.2018.9191