Correlation between the ETV6/CBFA2 (TEL/AML1) fusion gene and karyotypic abnormalities in children with B-cell precursor acute lymphoblastic leukemia.
The recently identified ETV6/CBFA2 (formerly known as TEL/AML1) fusion gene occurs as a result of the t(12;21)(p12;q22). Initial reports have indicated that the fusion transcript occurs in up to 30% of children diagnosed with B-cell precursor (CD10+, CD19+) acute lymphoblastic leukemia (ALL). In order to characterize the incidence of the t(12;21) at both the chromosomal level as well as the RNA transcript level, we have used a combination of classical cytogenetics, reverse transcriptase-polymerase chain reaction (RT-PCR), and fluorescence in situ hybridization (FISH) to examine the bone marrow of 34 children diagnosed with B-cell precursor ALL. Nine of the 34 patient samples expressed the ETV6/CBFA2 transcript. When the results of RT-PCR were compared with the conventional karyotype, the fusion was present in 3 of 10 (33%) with chromosome 12 abnormalities, none of whom had an obvious t(12;21). The transcript was also detected in 5 of the 12 (41%) bone marrow samples with other abnormalities and in 1 of 12 (8%) samples with a normal karyotype. Seven of the 9 RT-PCR positive patient samples were studied with FISH. Of the 7, FISH confirmed the ETV6/CBFA2 fusion in 6. One other patient with a 12p abnormality had evidence for the fusion using FISH which was not detected by RT-PCR. Our results not only confirm that the frequency of the t(12;21) is unusually high in childhood B-cell precursor ALL, but also that none of the translocations in our series was detected with conventional cytogenetic techniques.
Department of Molecular Genetics and Cellular Biology, University of Chicago, Illinois, USA.
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Fears
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Vignon
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Bohlander
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Smith
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Rowley
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Nucifora
D002051:Burkitt Lymphoma / Q000235:genetics*; D002648:Child; D002675:Child, Preschool; D002881:Chromosomes, Human, Pair 12; D050676:Core Binding Factor Alpha 2 Subunit; D005260:Female; D006801:Humans; D017404:In Situ Hybridization, Fluorescence; D007621:Karyotyping; D008297:Male; D009363:Neoplasm Proteins / Q000235:genetics*; D015514:Oncogene Proteins, Fusion; D016133:Polymerase Chain Reaction; D054198:Precursor Cell Lymphoblastic Leukemia-Lymphoma / Q000235:genetics; D012333:RNA, Messenger / Q000032:analysis; D012194:RNA-Directed DNA Polymerase; D014178:Translocation, Genetic; D000097764:ETS Translocation Variant 6 Protein
D050676:Core Binding Factor Alpha 2 Subunit; D009363:Neoplasm Proteins; D015514:Oncogene Proteins, Fusion; D012333:RNA, Messenger; D012194:RNA-Directed DNA Polymerase; C102421:TEL-AML1 fusion protein; D000097764:ETS Translocation Variant 6 Protein