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.
Fears
S
S
Department of Molecular Genetics and Cellular Biology, University of Chicago, Illinois, USA.
Vignon
C
C
Bohlander
S K
SK
Smith
S
S
Rowley
J D
JD
Nucifora
G
G
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