title: High-level amplification of the RUNX1 gene in two cases of childhood acute lymphoblastic leukemia.
abstract: The RUNX1 (alias AML1) gene is involved in several patterns of chromosomal translocations and rearrangements associated with human acute leukemia. Often, multiple signals for AML1 have been observed in childhood acute lymphoblastic leukemia (ALL) due to frequent polysomy of chromosome 21 in this leukemia. Additionally, high-level amplification of AML1, in the absence of polysomy of chromosome 21, has been reported in childhood ALL. We report two new cases of childhood ALL, without a ETV6/RUNX1 (alias TEL/AML1) rearrangement, showing high-level amplification of the AML1 gene detected by fluorescence in situ hybridization and comparative genomic hybridization analysis. The first case was an 11-year-old girl with 7-12 signals for AML1 in nearly 84% of the cells, and the loss of a TEL allele. In the second patient, a 6-year-old girl, multiple copies of the AML1 gene were also observed in 99% of the cells, although no deletion of TEL was found. The similarity in the clinicobiologic features of all the cases with this abnormality points to an emerging molecular cytogenetic subgroup of B-cell precursor ALL and suggests a possible dosage effect of AML1 in the pathogenesis of leukemia.
authors.affiliation: Hematology Service, University Hospital La Fe, Avenida Campanar, 21, Valencia, Spain.
authors.forename: Zaida
authors.initials: Z
authors.lastname: García-Casado
authors.forename: José
authors.initials: J
authors.lastname: Cervera
authors.forename: Amparo
authors.initials: A
authors.lastname: Verdeguer
authors.forename: Maria
authors.initials: M
authors.lastname: Tasso
authors.forename: Ana
authors.initials: A
authors.lastname: Valencia
authors.forename: Juan C
authors.initials: JC
authors.lastname: Pajuelo
authors.forename: Armando V
authors.initials: AV
authors.lastname: Mena-Duran
authors.forename: Eva
authors.initials: E
authors.lastname: Barragán
authors.forename: Margarita
authors.initials: M
authors.lastname: Blanes
authors.forename: Pascual
authors.initials: P
authors.lastname: Bolufer
authors.forename: Miguel A
authors.initials: MA
authors.lastname: Sanz
mesh_terms: D002648:Child; D050676:Core Binding Factor Alpha 2 Subunit / Q000235:genetics*; D005260:Female; D005784:Gene Amplification; D006801:Humans; D017404:In Situ Hybridization, Fluorescence; D054198:Precursor Cell Lymphoblastic Leukemia-Lymphoma / Q000235:genetics*
chemical_list: D050676:Core Binding Factor Alpha 2 Subunit; C493728:RUNX1 protein, human