Late-appearing pseudocentric fission event during chronic myeloid leukemia progression

Pseudocentric fission is a rare event consisting of the splitting of one functional centromere into two new products, of which only one can give rise to a functionally competent kinetochore. We report here a pseudocentric fission event within the D5Z2 alphoid subset disrupting the centromeric region of chromosome 5 in a case of chronic myeloid leukemia (CML) after treatment with imatinib and interferon. The breakage generated unequal partitioning of α-satellite sequences between the two fission products. One product was inserted within the long arm of chromosome 12 at band 14.3, becoming the only functional centromere of chromosome der(5). The other fission product was rearranged to form a sandwich-like dicentric—but functionally monocentric—chromosome der(6), made up of material from chromosomes 5, 12, and 6. The intercentric distance on der(6) was shown to be largely >20 Mb. To our knowledge, this is the first pseudocentric fission event described in CML. Moreover, our results confirm the susceptibility to breakage of the centromeric region of chromosome 5.