Deletions adjacent to BCR and ABL1 breakpoints occur in a substantial minority of chronic myeloid leukemia patients with masked Philadelphia rearrangements.

Deletions at the t(9;22) breakpoint regions, found in 15% of chronic myeloid leukemia patients (CML) with an overt Philadelphia (Ph) translocation, are associated with an adverse disease prognosis in patients receiving interferon-alpha therapy. 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. To date, however, the frequency of such deletions in the subgroup of CML patients in whom the BCR/ABL1 fusion arises via submicroscopic chromosomal insertion (masked Ph) has not been investigated. We report the evaluation of 14 patients with masked Ph-positive CML for the presence of deletions extending 3' from BCR and 5' from ABL1 using two triple-color BCR/ABL probes. Deletions were identified in 3 patients (21%), encompassing sequences 5' to ABL1 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.