On the genesis and prognosis of variant translocations in chronic myeloid leukemia

Variant translocations involving 9q, 22q, and at least one additional genomic locus occur in 5–10% of patients with chronic myeloid leukemia (CML). The mechanisms for the formation of these variant translocations are not fully characterized. Studies on the prognosis of these variant translocations revealed conflicting results. In addition, deletions in the derivative chromosome 9 are reportedly more frequent among variant translocation cases. We analyzed cytogenetic and FISH data from 22 CML patients with variant translocations tested at our laboratory. Deletions were observed in 6 of the 14 cases with FISH data available (43%), consistent with the literature and higher than in typical translocation cases (12–15%). Sequential changes of 9q deletions are possible and could be acquired as the disease progresses in addition to simultaneous formation of the Philadelphia chromosome with the deletion. Variant translocation CML patients with a deletion showed a worse cytogenetic response 1 year after therapy than those without a deletion (P < 0.05). Variant translocations may be formed by either a one-step or a two-step mechanism. Proper assessment of the prognostic significance of variant translocations requires better categorization of these translocations based on their mechanisms of genesis and the deletion status.