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).
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.
De Weer
An
A
Centre for Medical Genetics Gent (CMGG), Ghent University Hospital, Ghent, Belgium. an.deweer@ugent.be
Poppe
Bruce
B
Cauwelier
Barbara
B
Carlier
Andre
A
Dierick
Jan
J
Verhasselt
Bruno
B
Philippé
Jan
J
Van Roy
Nadine
N
Speleman
Frank
F
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
D004268:DNA-Binding Proteins; D000074008:MDS1 and EVI1 Complex Locus Protein; C063575:MECOM protein, human; D014157:Transcription Factors; D016044:Fusion Proteins, bcr-abl