Chronic myeloid leukaemia (CML) results from the malignant transformation of haematopoietic stem cells by the BCR-ABL fusion gene, generated by a reciprocal translocation between chromosomes 9 and 22, the Philadelphia (Ph) translocation, or variations thereof. Common permutations of the Ph include translocations involving one or more additional chromosomes to 9 and 22 (“variant” Ph), and rearrangements resulting in cryptic insertion of chromosome 9 into chromosome 22, or vice versa, leaving apparently normal chromosomes 9 and 22 (“masked” Ph). Recently the development of new FISH techniques led to the identification of unexpected deletions at the Ph translocation breakpoints in approximately 15% of CML patients. The deletions, encompassing sequences 3′ of the BCR breakpoint and/or 5′ of the ABL breakpoint, were associated with a shorter duration of chronic phase and shorter survival in patients treated with interferon therapy, although their impact in patients treated with tyrosine kinase inhibitors is currently unclear. Interestingly, the incidence of deletions has been shown to vary for different cytogenetic subgroups of CML, with a significantly higher incidence of deletion in patients with a variant Ph translocation. The frequency of such events in patients with masked Ph rearrangements, however, has not yet been explored because of limitations inherent to the widely adopted dual-colour BCR-ABL FISH approach. We report the evaluation of 14 patients with masked Ph-positive CML for the presence of deletions extending 3′ from BCR and 5′ from ABL using two 3-colour BCR-ABL probes. Deletions were identified in 3 patients in total (21%), encompassing sequences 5′ to ABL in two of these and sequences 3′ to BCR in the remaining patient, thus demonstrating that the phenomenon is a significant feature of the masked Ph CML subgroup. Furthermore, our findings are consistent with the notion that loss of genomic material is a potential side effect of any DNA breakage event at the 9q34.1 and 22q11.2 chromosomal regions, regardless of the subsequent mechanism of chromosomal rearrangement.

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