TEL-AML1 translocation in pediatric acute lymphoblastic leukemia : a study of target gene activation

Abstract

Acute Lymphoblastic Leukemia (A LL) is the most common cancer in childhood. Approximately 70% of these children are curable. Chromosomal translocations are important prognostic factors. Among B-precursor A LL, the cryptic translocation t(12;21 )(p13;q22) is common and is associated with a favorable outcome. The prevalence TEL-AM L 1 translocation in Thai children with A LL was previously unknown. The translocation results in fusion of the two genes, TEL(12p13) and AML 1(21q22). The chimeric TEL-AML 1 fusion gene generates the TEL-AML 1 fusion protein, which interferes with AM L1-dependent transcription and inhibits basal transcription from promoter or enhancer to the various target genes. This study aims to determine the prevalence of TEL-AML 1 in Thai children with ALL, and to determine the difference between TEL-AML 1 positive and TEL-AML 1 negative to the target genes. We collected bone marrow samples from 39 children newly-diagnosed with acute leukemia. After immunophenotype analysis, we selected 8-precursor ALL cases to study TEL-AML 1 expression and target gene expression. We found that TE L-AML 1 translocation was detectable in 9 (23%) of 39 Thai children with B-precursor ALL. We selected CD10+ CD19+ blast cells with immunomagnetic isolation and applied RT-PCR to analyze five known target genes of TEL-AML 1. We found that none of the genes were different in the expression, with the TEL-AML 1 positive group and the T EL-AM L 1 negative group (Fisher's exact tests). These were /L-3 (p=0.30), TCR (p=1.00), CR1 (p= 0.71), PKC (p=1.00), and RAG1. The target gene association showed the tendency relationship between IL-3 and CR1 (p=0.08) in TEL-AML 1 positive ALL, /L-3 and PKC (p=O 07) in TE L-AM L 1 negative ALL. Clinical relevance should be confirmed in a long-term study.