Prevalence of TEL/AML1 fusion gene in Thai children with B-cell precursor ALL using FISH technique

The prevalence of TEL/AML1 fusion (translocation ets leukemia/ acute myeloid leukemia 1) in Thai children with B-cell precursor acute lymphoblastic leukemia (ALL), fluorescence in situ hybridization (FISH) was determined in 31 patients. TEL/AML1 translocation was detected in 10 patients (32.3 %).  Other co-existing aberrations with TEL/AML1 were found including multiple copies of AML1 gene in 2  patients (6.4 %), TEL gene deletion in 5 patients (16.1 %).  TEL gene deletion was observed in association with extra copies of  AML1 in 1 case (3.2 %).  DNA  probe  specific  FISH  revealed  as  a  high-performance  tool to  exhibit  TEL/ AML1  fusion in B-cell precursor  childhood  ALL patients.  With  high incidence of TEL/ AML1 fusion  translocation  detected by FISH  in  this  study, further  areas  of chromosome  alterations  may  be  revealed  using  FISH  technique.     This should be beneficial in diagnostics and planning of treatment for the ALL patients.

Effect of genetic alterations of cytarabine-metabolizing enzymes in childhood acute lymphoblastic leukemia

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