title: Fluorescence in situ hybridization study of TEL/AML1 fusion and other abnormalities involving TEL and AML1 genes. Correlation with cytogenetic findings and prognostic value in children with acute lymphocytic leukemia.
abstract: OBJECTIVE
  The TEL/AML1 fusion is the most common genetic abnormality found in childhood acute lymphoblastic leukemias (ALL). Although it is very difficult to identify by conventional cytogenetic techniques it can be readily detected using fluorescence in situ hybridization (FISH). We carried out cytogenetic and FISH studies on 42 children with ALL in order to know the frequency of this translocation in our population, the incidence of TEL and/or AML1 gene alterations, and their correlation with clinical evolution and prognosis. In addition, we performed reverse transcription polymerase chain reaction (RT-PCR) in some cases, confirming the feasibility of FISH techniques in the detection of this translocation.
  
  
  METHODS
  Bone marrow samples were obtained from 42 childhood ALL patients. The copy number of AML1 and TEL genes were studied using fluorescent in situ hybridization with a dual color DNA probe specific for the AML1 and TEL genes.
  
  
  RESULTS
  We found a frequency of TEL/AML1 fusion of 17% in our sample. Double TEL/AML1 fusion, lack of TEL signal and extra AML1 signals were frequent additional FISH abnormalities. Duplication of a chromosomal complement, deletion of chromosome 12p arm, and polysomies of chromosome 21 are plausible explanations for these additional FISH findings. However, a relatively high proportion of our cases (9.5%) presented specific amplification of AML1. A statistically significant difference in prognosis was found between patients with and without these additional AML1 or TEL FISH alterations (p<0.02), which could be related to the presence of specific karyotypes.
  
  
  CONCLUSIONS
  The frequency of TEL/AML1 fusion is similar to that found in other populations (17%). We found that FISH analysis of AML and TEL is related to the evolution of the disease. The absence of alterations in these genes revealed by FISH could be indicative of bad prognosis, while the presence of alterations is related to a good evolution. Our results suggest that interphase FISH analysis to search for alterations in AML and TEL genes could be extremely useful for complementing cytogenetic studies and for providing additional information about the possible outcome of the disease in patients with ALL.
authors.affiliation: Dpto. de Genética Humana, Programa de Patología Molecular, Centro Nacional de Investigaciones Oncológicas (CNIO), Ctra. Majadahonda-Pozuelo, Km. 2, 28220 Majadahonda, Madrid, Spain. angmartinez@cnio.es
authors.forename: A
authors.initials: A
authors.lastname: Martínez-Ramírez
authors.forename: M
authors.initials: M
authors.lastname: Urioste
authors.forename: T
authors.initials: T
authors.lastname: Contra
authors.forename: A
authors.initials: A
authors.lastname: Cantalejo
authors.forename: A
authors.initials: A
authors.lastname: Tavares
authors.forename: J A
authors.initials: JA
authors.lastname: Portero
authors.forename: B
authors.initials: B
authors.lastname: López-Ibor
authors.forename: M
authors.initials: M
authors.lastname: Bernacer
authors.forename: C
authors.initials: C
authors.lastname: Soto
authors.forename: J C
authors.initials: JC
authors.lastname: Cigudosa
authors.forename: J
authors.initials: J
authors.lastname: Benítez
mesh_terms: D000293:Adolescent; D001853:Bone Marrow; D002648:Child; D002675:Child, Preschool; D002869:Chromosome Aberrations; D050676:Core Binding Factor Alpha 2 Subunit; D020732:Cytogenetic Analysis; D004268:DNA-Binding Proteins / Q000235:genetics; D005260:Female; D018628:Gene Dosage; D006801:Humans; D017404:In Situ Hybridization, Fluorescence; D008297:Male; D015514:Oncogene Proteins, Fusion / Q000235:genetics*; D054198:Precursor Cell Lymphoblastic Leukemia-Lymphoma / Q000175:diagnosis / Q000235:genetics*; D011379:Prognosis; D011518:Proto-Oncogene Proteins; D050783:Proto-Oncogene Proteins c-ets; D012097:Repressor Proteins / Q000235:genetics; D014157:Transcription Factors / Q000235:genetics; D000097764:ETS Translocation Variant 6 Protein
chemical_list: D050676:Core Binding Factor Alpha 2 Subunit; D004268:DNA-Binding Proteins; D015514:Oncogene Proteins, Fusion; D011518:Proto-Oncogene Proteins; D050783:Proto-Oncogene Proteins c-ets; D012097:Repressor Proteins; D014157:Transcription Factors; D000097764:ETS Translocation Variant 6 Protein; C493728:RUNX1 protein, human; C102421:TEL-AML1 fusion protein