title: 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.
authors.affiliation: LRF Cytogenetics Group, Cancer Sciences Division, University of Southampton, United Kingdom. m.martineau@soton.ac.uk
authors.forename: Mary
authors.initials: M
authors.lastname: Martineau
authors.forename: G Reza
authors.initials: GR
authors.lastname: Jalali
authors.forename: Kerry E
authors.initials: KE
authors.lastname: Barber
authors.forename: Zoë J
authors.initials: ZJ
authors.lastname: Broadfield
authors.forename: Kan Luk
authors.initials: KL
authors.lastname: Cheung
authors.forename: John
authors.initials: J
authors.lastname: Lilleyman
authors.forename: Anthony V
authors.initials: AV
authors.lastname: Moorman
authors.forename: Sue
authors.initials: S
authors.lastname: Richards
authors.forename: Hazel M
authors.initials: HM
authors.lastname: Robinson
authors.forename: Fiona
authors.initials: F
authors.lastname: Ross
authors.forename: Christine J
authors.initials: CJ
authors.lastname: Harrison
mesh_terms: D000293:Adolescent; D000328:Adult; D019677:Artificial Gene Fusion; D002648:Child; D002675:Child, Preschool; D002874:Chromosome Mapping; D050676:Core Binding Factor Alpha 2 Subunit; D004268:DNA-Binding Proteins / Q000235:genetics*; D005260:Female; D006801:Humans; D017404:In Situ Hybridization, Fluorescence; D007223:Infant; D007621:Karyotyping; D008297:Male; D008875:Middle Aged; D009687:Nuclear Proteins / Q000235:genetics*; D054198:Precursor Cell Lymphoblastic Leukemia-Lymphoma / Q000175:diagnosis / Q000235:genetics*; D011379:Prognosis; D011518:Proto-Oncogene Proteins / Q000235:genetics*; D050783:Proto-Oncogene Proteins c-ets; D012008:Recurrence; 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; D009687:Nuclear Proteins; 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