Centrosome aberrations in chronic myeloid leukemia correlate with stage of disease and chromosomal instability.

ABSTRACT

Centrosome abnormalities are hallmarks of various cancers and have been implicated in chromosome missegregation, chromosomal instability, and aneuploidy. Since genetic instability is a common feature in chronic myeloid leukemia (CML), we sought to investigate whether centrosome aberrations occur and correlate with disease stage and cytogenetic findings in CML. We examined 34 CML samples including CD 34+Ph+cells of 18 newly diagnosed patients (chronic phase (CP)) and 16 blast crisis (BC) specimens by using a centrosome-specific antibody to pericentrin. All CP and BC samples displayed centrosome alterations as compared with corresponding CD 34+control cells. Centrosome abnormalities were detected in 29.1+/-5.9% of CP blasts and in 54.3+/-4.8% of BC blasts, but in only 2.4+/-1.1% of controls (P<0.0001). Additional karyotypic alterations to the t(9;22) translocation were found in only 1/18 CML-CP patients. In contrast, 11/16 (73%) CML-BC patients displayed additional karyotype alterations in 48.7% of analyzed cells, correlating with an abnormal centrosome status (P=0.0005). Our results indicate that centrosome defects are a common and early detectable feature in CML that may contribute to acquisition of chromosomal aberrations and aneuploidy. They may be considered as the driving force of disease progression and could serve as future prognostic markers.