Impact of single nucleotide polymorphisms of cytarabine metabolic genes on drug toxicity in childhood acute lymphoblastic leukemia

Krisztina Mita Gabor, Geza Schermann, Orsolya Lautner-Csorba, Ferenc Rarosi, Daniel J. Erdelyi, Emoke Endreffy, Krisztina Berek, Katalin Bartyik, Csaba Bereczki, Csaba Szalai, Agnes F. Semsei

Research output: Contribution to journalArticle

8 Citations (Scopus)

Abstract

Background: Cytarabine (cytosine arabinoside, ara-C) is a chemotherapeutical agent used in the treatment of pediatric acute lymphoblastic leukemia (ALL). Adverse drug reactions, such as interpatient variability in sensitivity to ara-C, are considerable and may cause difficulties during chemotherapy. Single nucleotide polymorphisms (SNPs) can play a significant role in modifying nucleoside-drug pharmacokinetics and pharmacodynamics and thus the development of adverse effects. Our aim was to determine whether polymorphisms in genes encoding transporters and enzymes responsible for the metabolism of ara-C are associated with toxicity and clinical outcome in a patient population with childhood ALL. Procedure: We studied 8 SNPs in the CDA, DCK, DCTD, SLC28A3, and SLC29A1 genes in 144 patients with childhood acute lymphoblastic leukemia treated according to ALLIC BFM 1990, 1995 and 2002 protocols. Results: DCK rs12648166 and DCK rs4694362 SNPs were associated with hematologic toxicity (OR = 2.63, CI 95% = 1.37-5.04, P=0.0036 and OR = 2.53, CI 95% = 1.34-4.80, P=0.0044, respectively). Conclusions: Our results indicate that DCK polymorphisms might be important genetic risk factors for hematologic toxicity during ALL treatment with ara-C. Individualized chemotherapy based on genetic profiling may help to optimize ara-C dosing, leading to improvements in clinical outcome and reduced toxicity. Pediatr Blood Cancer 2015;62:622-628.

Original languageEnglish
Pages (from-to)622-628
Number of pages7
JournalPediatric Blood and Cancer
Volume62
Issue number4
DOIs
Publication statusPublished - Apr 1 2015

Keywords

  • Childhood acute lymphoblastic leukemia
  • Cytarabine
  • DCK
  • Single nucleotide polymorphism
  • Toxicity

ASJC Scopus subject areas

  • Pediatrics, Perinatology, and Child Health
  • Hematology
  • Oncology

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