Pharmacogenetic markers in the therapy of childhood acute lymphoblastic leukemia

  • Alenka Šmid Faculty of Pharacy, University of Ljubljana, Ljubljana, Slovenia
  • Janez Jazbec Unit of Oncology and Haematology, Division of Paediatrics, University Medical Centre Ljubljana, Ljubljana, Slovenia
  • Irena Mlinarič-Raščan Univerza v Ljubljani, Fakulteta za farmacijo
Keywords: Personalized medicine, Pharmacogenetics, Acute Lymphoblastic Leukaemia, Thiopurine-S-methyltransferase, thiopurines

Abstract

Personalised medicine is a contemporary concept in medical practice, based on the observation that individuals respond differently to a particular therapy. Biomarkers, which include genetic markers, are a central element in the development of personalised medicine. Acute lymphoblastic leukaemia (ALL) therapy is among the most successful examples of the implementation of pharmacogenetic markers into clinical practice in order to adjust the dosage of drugs to an individual. ALL accounts for approximately 80% of all forms of leukaemia occurring in children under the age of 15 years, making it the most common childhood cancer. Despite drastic improvements in the treatment of childhood ALL over the past decades, treatment is still unsuccessful in some patients either due to toxic effects, or due to the inefficacy of the drugs used, which leads to a recurrence of the disease. An additional problem is associated with the long-term toxic effects of chemotherapy, which may occur several years after the treatment has been completed. In order to improve safety and efficacy, numerous studies have been performed aiming to identify biomarkers which would enable tailoring treatment to the individual patient and improve treatment’s efficacy and safety.

Of these, the genetic factors associated with the toxicity of 6-mercaptopurine (6-MP), which is the cornerstone of maintenance treatment of ALL, have been studied most thoroughly. Thiopurine S- methyltransferase (TPMT) is a polymorphic enzyme which plays a major role in the deactivation of thiopurines and to a large extent accounts for the differences in individuals’ response to treatment. It has long been known that polymorphisms in the TPMT gene are largely responsible for reduced enzymatic activities, but numerous studies have shown that the accordance between genotype and enzyme activity is incomplete. In many studies published over the past decade, new pharmacogenetic markers have been associated with toxic effects of 6-MP as well as other drugs used for ALL therapy; however, they are not yet used in clinical practice.

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Published
2019-07-10
How to Cite
1.
Šmid A, Jazbec J, Mlinarič-Raščan I. Pharmacogenetic markers in the therapy of childhood acute lymphoblastic leukemia. TEST ZdravVestn [Internet]. 10Jul.2019 [cited 29Mar.2024];88(5-6):235-48. Available from: http://vestnik-dev.szd.si/index.php/ZdravVest/article/view/2851