Pharmacogenomic markers of glucocorticoid response in the initial phase of remission induction therapy in childhood acute lymphoblastic leukemia

  • Vladimir Gasic Laboratory for Molecular Biomedicine Institute of Molecular Genetics and Genetic Engineering University of Belgrade
  • Branka Zukic Laboratory for Molecular Biomedicine Institute of Molecular Genetics and Genetic Engineering University of Belgrade
  • Biljana Stankovic Laboratory for Molecular Biomedicine Institute of Molecular Genetics and Genetic Engineering University of Belgrade
  • Dragana Janic Department of Hematology and Oncology, University Children’s Hospital, University of Belgrade
  • Lidija Dokmanovic Department of Hematology and Oncology, University Children’s Hospital, University of Belgrade
  • Jelena Lazic Department of Hematology and Oncology, University Children’s Hospital, University of Belgrade
  • Nada Krstovski Department of Hematology and Oncology, University Children’s Hospital, University of Belgrade
  • Vita Dolzan Pharmacogenetics Laboratory, Institute of Biochemistry, Faculty of Medicine, University of Ljubljana
  • Janez Jazbec Department of Oncology and Haematology, University Children’s Hospital, University Medical Centre Ljubljana
  • Sonja Pavlovic Laboratory for Molecular Biomedicine, Institute of Molecular Genetics and Genetic Engineering, University of Belgrade
  • Nikola Kotur Laboratory for Molecular Biomedicine Institute of Molecular Genetics and Genetic Engineering University of Belgrade

Abstract

Aims: Response to glucocorticoid (GC) monotherapy in the initial phase of remission induction treatment in childhood acute lymphoblastic leukemia (ALL) represents important biomarker of prognosis and outcome. We aimed to study variants in several pharmacogenes (NR3C1, GSTs and ABCB1) that could contribute to improvement of GC response through personalization of GC therapy. The marker of GC response is blast count per microliter of peripheral blood on treatment day 8. We carried out analysis in which cut-off value for GC response was 1000 (according to BFM protocol), as well as 100 or 0 blasts per microliter.

Methods: Retrospective study enrolling 122 ALL patients was carried out to analyze variants of NR3C1 (rs33389, rs33388 and rs6198), GSTT1 (null genotype), GSTM1 (null genotype), GSTP1 (rs1695 and rs1138272) and ABCB1 (rs1128503, rs2032582 and rs1045642) genes using PCR-based methodology.

Results: Carriers of rare NR3C1 rs6198 GG genotype were more likely to have blast count over 1000, than the non-carriers (p=0.030). NR3C1 CAA (rs33389-rs33388-rs6198) haplotype was associated with blast number below 1000 (p=0.030). GSTP1 GC haplotype carriers were more likely to have blast number below 1000 (p=0.036), below 100 (p=0.028) and to be blast negative (p=0.054), while GSTP1 GT haplotype and rs1138272 T allele carriers were more likely to be blasts positive (p=0.034 and p=0.024, respectively). ABCB1 CGT (rs1128503-rs2032582-rs1045642) haplotype carriers were more likely to be blast positive (p=0.018).

Conclusion: Our results have shown that NR3C1 rs6198 variant and GSTP1 rs1695-rs1138272 haplotype are the most promising pharmacogenomic markers of GC response in ALL patients.

Published
2018-09-06
How to Cite
Gasic, V., Zukic, B., Stankovic, B., Janic, D., Dokmanovic, L., Lazic, J., Krstovski, N., Dolzan, V., Jazbec, J., Pavlovic, S., & Kotur, N. (2018). Pharmacogenomic markers of glucocorticoid response in the initial phase of remission induction therapy in childhood acute lymphoblastic leukemia. Radiology and Oncology, 52(3). Retrieved from https://radioloncol.com/index.php/ro/article/view/3015
Section
Clinical oncology