Effect of genetic alterations of cytarabine-metabolizing enzymes in childhood acute lymphoblastic leukemia
Hematology, Oncology and Stem Cell Therapy. 2010; 3 (3): 103-108
em Inglês
| IMEMR
| ID: emr-129184
ABSTRACT
Single nucleotide polymorphisms [SNPs] of deoxyctidine kinase [dCK] and cytidine deaminase [CDA] are known to alter their enzymatic activities, which affect the metabolism of cytarabine. Currently, treatment of childhood acute lymphoblastic leukemia [ALL] includes cytarabine, especially in high-risk patients. Therefore we hypothesized that a genetic variation of dCK and CDA genes may influence the risk of cytarabine-related toxicities and early response to treatment. We included children diagnosed with ALL and lymphoblastic lymphoma [LL] stage III and IV. The patients received a modified ST Jude Total Therapy Study XV protocol. Cytarabine was used during induction remission [low-dose cytarabine] and reinduction II [high-dose cytarabine] phases. Genotyping of dCK -360 > G and -201 > T and CDA 79A > C and 208G > A was performed. Minimal residual disease [MRD] at the end of the induction phase was measured using flow cytomery. Ninety-four children with ALL [n=90] and LL [n=4] were analyzed. The median age at diagnosis was 5.8 years [range, 0.4-15 years]. All four SNPs showed predominant wild type alleles. There was no CDA-208A allele in our population. Children with dCK-360G allele were at risk of mycositis after receiving low-dose cytarabine [OR=3.7; 95% CI, 1.2-11.3]. Neither dCK nor CDA polymorphisms affected the MRD status at the end of induction phase. The dCK-360G allele was found to found to increase the risk of mucositis after expose to low-dose cytarabine in childhood ALL therapy
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Índice:
IMEMR (Mediterrâneo Oriental)
Assunto principal:
Criança
/
Citidina Desaminase
/
Desoxicitidina Quinase
/
Leucemia-Linfoma Linfoblástico de Células Precursoras
/
Genótipo
Limite:
Feminino
/
Humanos
/
Masculino
Idioma:
Inglês
Revista:
Hematol. Oncol. Stem Cell Ther.
Ano de publicação:
2010
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