ABSTRACT
Akin DF, Aslar-Öner D, Kürekçi E, Akar N. Frequency of thiopurine S-methyltransferase gene variations in Turkish children with acute leukemia. Turk J Pediatr 2018; 60: 147-152. In this study we aim to determine the genotype distribution and allele frequencies of common TPMT (*2, *3A, *3B and *3C) polymorphisms in Turkish children with acute leukemia. The study population consisted of 169 patients aged between 1 and 15 years who were admitted to Losante Pediatric Hematology and Children`s Hospital with the diagnosis of acute leukemia. Genotyping of TPMT polymorphisms was screened with real-time PCR using fluorescence melting curve detection analysis. We found that the frequencies of four allelic variants of TPMT are *2 (238 G > C) (0,0%), *3A (460G > A and 719A > G) (1.7%), *3B (460G > A) (1,7%) and *3C (719A > G) (2.4%). Frequency of TPMT alleles increases the efficacy of leukemia treatment. Thus, TPMT genotyping can be useful for optimizing 6-MP therapy.
Subject(s)
Leukemia/genetics , Methyltransferases/genetics , Acute Disease , Adolescent , Alleles , Child , Child, Preschool , Female , Gene Frequency , Genotype , Humans , Infant , Male , Polymorphism, Genetic , Real-Time Polymerase Chain Reaction , TurkeyABSTRACT
BACKGROUND: CD22 is expressed on the surface of B-cell lineage cells from the early progenitor stage of pro-B cell until terminal differentiation to mature B cells. It plays a role in signal transduction and as a regulator of B-cell receptor signaling in B-cell development. OBJECTIVES: We aimed to screen exons 9-14 of the CD22 gene, which is a mutational hot spot region in B-precursor acute lymphoblastic leukemia (pre-B ALL) patients, to find possible genetic variants that could play role in the pathogenesis of pre-B ALL in Turkish children. METHODS: This study included 109 Turkish children with pre-B ALL who were diagnosed at Losante Hospital for Children with Leukemia. Genomic DNA was extracted from both peripheral blood and bone marrow leukocytes. Gene amplification was performed with PCR, and all samples were screened for the variants by single strand conformation polymorphism. Samples showing band shifts were sequenced on an automated sequencer. RESULTS: In our patient group a total of 9 variants were identified in the CD22 gene by sequencing: a novel variant in intron 10 (T2199G); a missense variant in exon 12; 5 intronic variants between exon 12 and intron 13; a novel intronic variant (C2424T); and a synonymous in exon 13. Thirteen of 109 children (11.9%) carried the T2199G novel intronic variant located in intron 10, and 17 of 109 children (15.6%) carried the C2424T novel intronic variant. CONCLUSION: Novel variants in the CD22 gene in children with pre-B ALL in Turkey that are not present, in the Human Gene Mutation Database or NCBI SNP database, were found.
Subject(s)
Precursor B-Cell Lymphoblastic Leukemia-Lymphoma/genetics , Precursor Cell Lymphoblastic Leukemia-Lymphoma/genetics , Sialic Acid Binding Ig-like Lectin 2/genetics , Adolescent , Base Sequence , Child , Child, Preschool , Exons , Female , Genetic Variation , Humans , Infant , Introns , Male , Mutation , Polymorphism, Genetic , Precursor B-Cell Lymphoblastic Leukemia-Lymphoma/metabolism , Precursor Cell Lymphoblastic Leukemia-Lymphoma/metabolism , Sialic Acid Binding Ig-like Lectin 2/metabolism , TurkeyABSTRACT
This study was undertaken to determine the prevalence of the Factor V 1691 G-A and PT 20210 G-A mutations in Turkish children with leukemia. We genotyped 135 pediatric leukemia patients with for these mutations. Eleven (8%) of the 135 patients were heterozygous for the FV 1691 G-A mutation. Seven (5,1%) of the patients carried the PT 20210 G-A heterozygous mutation. Of the 135 patients, only three had thrombotic event, none of which had these two mutations, which is common in Turkish population. Our findings revealed a controversial compared to the previous reports, which needs further investigation.