EVII 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 EVII locus. Methods: Dual-colour Fluorescence In Situ Hybridisation was performed to unravel the different cytogenetic aberrations. Expression levels of EVII and BCR/ABLI 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/ABLI gene fusion, also resulted in EVII rearrangement and overexpression. Conclusion: 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