title: AML1 gene amplification: a novel finding in childhood acute lymphoblastic leukemia.
abstract: OBJECTIVE
  We previously found a high-level amplification in chromosomal region 21q22 in two children with acute lymphoblastic leukemia (ALL) using comparative genomic hybridization. The same region harbors the AML1 gene. The aim of the present study was to investigate whether AML1 is a target gene in these amplifications.
  
  
  METHODS
  Bone marrow samples were obtained from 112 childhood ALL patients. The copy number of AML1 was studied using fluorescent in situ hybridization with a dual color DNA probe specific for the AML1 and TEL genes.
  
  
  RESULTS
  Three of the patients had 3-to-8 fold amplification of AML1 and showed a high-level amplification of 21q22 by comparative genomic hybridization. In two of them the extra copies were shown to be located tandemly in a derivative of chromosome 21. Thirty-seven of the patients (33%) had 1-to-2 extra copies of AML1, most probably reflecting the incidence of trisomy 21 and tetrasomy 21. The TEL-AML1 fusion was less frequent in the patients with extra copies of AML1 (7/40; 18%) than in the patients with no extra copy (24/72; 33%). None of the three patients with 3-to-8 fold amplification of AML1 showed the fusion or loss of TEL.
  
  
  CONCLUSIONS
  Our findings suggest that the AML1 gene is a target gene in the 21q22 amplicon in childhood ALL. To understand the role, if any, of the AML1 amplification in leukemogenesis, further studies are needed.
authors.affiliation: Department of Medical Genetics, Haartman Institute and Helsinki University Central Hospital, University of Helsinki, Helsinki, Finland.
authors.forename: T
authors.initials: T
authors.lastname: Niini
authors.forename: J
authors.initials: J
authors.lastname: Kanerva
authors.forename: K
authors.initials: K
authors.lastname: Vettenranta
authors.forename: U M
authors.initials: UM
authors.lastname: Saarinen-Pihkala
authors.forename: S
authors.initials: S
authors.lastname: Knuutila
mesh_terms: D000293:Adolescent; D001854:Bone Marrow Cells / Q000378:metabolism; D002648:Child; D002675:Child, Preschool; D002891:Chromosomes, Human, Pair 21; D050676:Core Binding Factor Alpha 2 Subunit; D004268:DNA-Binding Proteins / Q000235:genetics*; D005260:Female; D005784:Gene Amplification / Q000235:genetics; D018628:Gene Dosage; D006801:Humans; D017404:In Situ Hybridization, Fluorescence; D007223:Infant; D008297:Male; D009363:Neoplasm Proteins / Q000235:genetics; D054198:Precursor Cell Lymphoblastic Leukemia-Lymphoma / Q000235:genetics*; D011518:Proto-Oncogene Proteins; D014157:Transcription Factors / Q000235:genetics*
chemical_list: D050676:Core Binding Factor Alpha 2 Subunit; D004268:DNA-Binding Proteins; D009363:Neoplasm Proteins; D011518:Proto-Oncogene Proteins; C493728:RUNX1 protein, human; D014157:Transcription Factors