Abstract
BackgroundVariant 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.MethodsDual-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.ResultsIn 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.ConclusionThis 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.
Highlights
Variant translocations t(9;22) occur in 5 to 10% of newly diagnosed Chronic myeloid leukemia (CML) and additional genetic changes are present in 60–80% of patients in blast crisis (BC)
We describe how the molecular characterization of the translocation breakpoints of a variant t(9;22) in a patient with CML in blast crisis lead to the discovery of involvement of the Ecotropic Viral Integration site 1 (EVI1) locus
We describe the molecular characterization of a complex 4-way t(3;9;17;22) translocation, which in addition to Breakpoint Cluster Region (BCR)-ABeLson murine leukemia viral oncogene homolog 1 (ABL1) gene fusion resulted in EVI1 overexpres
Summary
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). We report on a CML patient in blast crisis presenting with a four-way variant t(9;22) rearrangement involving the EVI1 locus. The typical associated translocation t(9;22)(q34;q11), leading to the BCR/ABL1 fusion gene and constitutive activation of the ABL1 tyrosine kinase on 9q34, is considered to be the initial transforming event [1]. CML in blast crisis is often accompanied by the presence of additional chromo-. Activation of the EVI1 gene has been reported in a small percentage of patients [3]. Ectopic expression of the EVI1 gene is usually due to recurrent 3q26 translocations such as the t(3;21)(q26;q22)
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
