ETV6/RUNX1 fusion at diagnosis and relapse: some prognostic indications (2005)

Author(s): Martineau M, Jalali GR, Barber KE, Broadfield ZJ, Cheung KL, Lilleyman J, Moorman AV, Richards S, Robinson HM, Ross F, Harrison CJ

  • : ETV6/RUNX1 fusion at diagnosis and relapse: some prognostic indications

Abstract: This study was undertaken in order to compare the interphase and metaphase cytogenetics of 28 patients with ETV6/RUNX1 positive acute lymphoblastic leukemia, at diagnosis and relapse. The median time to relapse was 26 months. The significant fusion positive population heterogeneity revealed at interphase by a commercial probe for ETV6/RUNX1 fusion has not been described before. Six diagnostic samples had a single abnormal population; others had up to five each, which differed in the numbers of RUNX1 signals, and in the retention or loss of the second ETV6 signal. In contrast, the number of fusion signals was more constant. At relapse, there were fewer populations; the largest or unique clone was sometimes a re-emergence of a minor, diagnostic one, with a retained copy of ETV6 and the most RUNX1 signals. Abnormal, fusion negative clones were identified in bone marrow samples at extra-medullary relapse. Variant three or four-way translocations, which involved chromosomes 12 and 21, were prominent among the complex rearrangements revealed by metaphase FISH. The frequency of their occurrence at diagnosis and reappearance at relapse, sometimes accompanied by minor clonal evolution, was another new observation. Other recurrent cytogenetic features included a second copy of the fusion signal in six cases, partial duplication of the long arm of the X chromosome in two cases, and trisomy 10 in three cases. In comparing our data with previously reported cases, a picture is beginning to emerge of certain diagnostic features, which may provide circumstantial evidence of an increased risk of relapse.

Notes: Journal Article Research Support, Non-U.S. Gov't United States

  • Short Title: ETV6/RUNX1 fusion at diagnosis and relapse: some prognostic indications
  • Alternate Journal: Genes, chromosomes & cancer
  • Date: 09-02-2005
  • Journal: Genes, Chromosomes and Cancer
  • Volume: 43
  • Issue: 1
  • Pages: 54-71
  • Publication type: Article
  • Bibliographic status: Published

Keywords: Adolescent Adult *Artificial Gene Fusion Child Child, Preschool Chromosome Mapping Core Binding Factor Alpha 2 Subunit DNA-Binding Proteins/*genetics Female Humans In Situ Hybridization, Fluorescence Infant Karyotyping Male Middle Aged Nuclear Proteins/*genetics Precursor Cell Lymphoblastic Leukemia-Lymphoma/diagnosis/*genetics Prognosis Proto-Oncogene Proteins/*genetics Proto-Oncogene Proteins c-ets Recurrence Repressor Proteins/*genetics Transcription Factors/*genetics


Professor Anthony Moorman
Professor of Genetic Epidemiology