title: EVI1 activation in blast crisis CML due to juxtaposition to the rare 17q22 partner region as part of a 4-way variant translocation t(9;22).
abstract: BACKGROUND
  Variant translocations t(9;22) occur in 5 to 10% of newly diagnosed CMLs and additional genetic changes are present in 60-80% of patients in blast crisis (BC). Here, we report on a CML patient in blast crisis presenting with a four-way variant t(9;22) rearrangement involving the EVI1 locus.
  
  
  METHODS
  Dual-colour Fluorescence In Situ Hybridisation was performed to unravel the different cytogenetic aberrations. Expression levels of EVI1 and BCR/ABL1 were investigated using real-time quantitative RT-PCR.
  
  
  RESULTS
  In this paper we identified a patient with a complex 4-way t(3;9;17;22) which, in addition to BCR/ABL1 gene fusion, also resulted in EVI1 rearrangement and overexpression.
  
  
  CONCLUSIONS
  This report illustrates how a variant t(9;22) translocation can specifically target a second oncogene most likely contributing to the more aggressive phenotype of the disease. Molecular analysis of such variants is thus warranted to understand the phenotypic consequences and to open the way for combined molecular therapies in order to tackle the secondary oncogenic effect which is unresponsive to imatinib treatment.
authors.affiliation: Centre for Medical Genetics Gent (CMGG), Ghent University Hospital, Ghent, Belgium. an.deweer@ugent.be
authors.forename: An
authors.initials: A
authors.lastname: De Weer
authors.forename: Bruce
authors.initials: B
authors.lastname: Poppe
authors.forename: Barbara
authors.initials: B
authors.lastname: Cauwelier
authors.forename: Andre
authors.initials: A
authors.lastname: Carlier
authors.forename: Jan
authors.initials: J
authors.lastname: Dierick
authors.forename: Bruno
authors.initials: B
authors.lastname: Verhasselt
authors.forename: Jan
authors.initials: J
authors.lastname: Philippé
authors.forename: Nadine
authors.initials: N
authors.lastname: Van Roy
authors.forename: Frank
authors.initials: F
authors.lastname: Speleman
mesh_terms: D001752:Blast Crisis / Q000235:genetics*; D002869:Chromosome Aberrations; D002892:Chromosomes, Human, Pair 22; D002893:Chromosomes, Human, Pair 3; D002899:Chromosomes, Human, Pair 9; D020732:Cytogenetic Analysis; D004268:DNA-Binding Proteins / Q000235:genetics* / Q000378:metabolism; D016044:Fusion Proteins, bcr-abl / Q000096:biosynthesis / Q000235:genetics*; D015973:Gene Expression Regulation, Leukemic; D016313:Genes, abl / Q000235:genetics; D006801:Humans; D015464:Leukemia, Myelogenous, Chronic, BCR-ABL Positive / Q000235:genetics* / Q000473:pathology* / Q000628:therapy; D000074008:MDS1 and EVI1 Complex Locus Protein; D010677:Philadelphia Chromosome; D011519:Proto-Oncogenes / Q000235:genetics*; D014157:Transcription Factors / Q000235:genetics* / Q000378:metabolism; D015533:Transcriptional Activation
chemical_list: D004268:DNA-Binding Proteins; D000074008:MDS1 and EVI1 Complex Locus Protein; C063575:MECOM protein, human; D014157:Transcription Factors; D016044:Fusion Proteins, bcr-abl