title: ETV6/CBFA2 fusions in childhood B-cell precursor acute lymphoblastic leukemia with myeloid markers.
abstract: A translocation resulting in a fusion of ETV6 (TEL) gene at 12p13 and CBFA2 (AML1) gene at 21q22 is variably reported in 16-36% of cases of childhood acute lymphoblastic leukemia (ALL). This t(12;21)(p13;q22) is not detectable by conventional cytogenetic methods and was reported to be associated with B-cell precursor ALL with presumed favorable prognosis. We have examined 18 cases of well characterized childhood B-cell precursor ALL with cytogenetic, immunophenotypic, and clinical data for the presence of the t(12;21) using fluorescence in situ hybridization (FISH). Fourteen of the 18 cases (78%) were positive for fusion ETV6/CBFA2. One of seven adult ALL patients was positive (12% of cells positive in this 21 year old patient). By contrast, no evidence of t(12;21) by FISH was noted in two childhood T-ALL cases and 10 normal bone marrow samples. Twelve of the 14 positive childhood cases had CD13 and/or CD33 expression (myeloid markers) while only one of the four negative cases was CD13 and CD33 positive. Eight of 12 cases positive for t(12;21), and with conventional cytogenetic data, had structural and/or numerical chromosome abnormalities other than the detected t(12;21). One case had relapse with gradual increase in percentage of cells positive for t(12;21) and development of an isochromosome 21 carrying the fusion signals. The data reveal a strong association of t(12;21) with B-cell precursor ALL, especially with myeloid marker expression.
authors: Genetics Department, Yale University School of Medicine, New Haven, Connecticut 06520-8005, USA.
authors: S K
authors: SK
authors: Rafi
authors: H
authors: H
authors: El Gebaly
authors: M B
authors: MB
authors: Qumsiyeh
mesh_terms: D000293:Adolescent; D000328:Adult; D014408:Biomarkers, Tumor / Q000235:genetics*; D002051:Burkitt Lymphoma / Q000175:diagnosis / Q000235:genetics* / Q000473:pathology; D002648:Child; D002675:Child, Preschool; D050676:Core Binding Factor Alpha 2 Subunit; D005260:Female; D006801:Humans; D017404:In Situ Hybridization, Fluorescence; D007223:Infant; D008297:Male; D023461:Myeloid Progenitor Cells / Q000737:chemistry / Q000473:pathology*; D015514:Oncogene Proteins, Fusion / Q000235:genetics*; D054198:Precursor Cell Lymphoblastic Leukemia-Lymphoma / Q000175:diagnosis / Q000235:genetics* / Q000473:pathology; D014178:Translocation, Genetic; D000097764:ETS Translocation Variant 6 Protein
chemical_list: D014408:Biomarkers, Tumor; D050676:Core Binding Factor Alpha 2 Subunit; D015514:Oncogene Proteins, Fusion; C102421:TEL-AML1 fusion protein; D000097764:ETS Translocation Variant 6 Protein