Genomic deletions on other chromosomes involved in variant t(9;22) chronic myeloid leukemia cases

The Philadelphia (Ph) chromosome is the cytogenetic hallmark of chronic myeloid leukemia (CML) and is observed in more than 90% of CML cases. At diagnosis, in 5-10% of CML patients the Ph chromosome is derived from variant translocations other than the standard t(9;22). Deletions adjacent to the translocation junction on the derivative chromosome 9 were recently described by different groups. The deletions may identify a subgroup with a worse prognosis. The presence of similar deletions on the third derivative other than the 9 and 22 chromosomes in CML with variant translocation has never been investigated. We studied three cases of CML variants showing relatively large deletions on the third chromosome involved in the translocation. Known tumor-suppressor genes (TSGs) or genes involved in signal transduction and in the modulation of cell proliferation were found to be located inside these deleted regions. As an alternative to Knudson's two-hit model, the "haplo-insufficiency" hypothesis suggests that the deletion of a single allele of a TSG can play an important role in tumor progression. Our findings suggest that great attention should be paid to the molecular cytogenetic characterization of variant t(9;22) CML patients to unveil fully the biological heterogeneity of CML.