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- Title
Centrosome aberrations after nilotinib and imatinib treatment in vitro are associated with mitotic spindle defects and genetic instability.
- Authors
Fabarius, Alice; Giehl, Michelle; Frank, Oliver; Spiess, Birgit; Zheng, Chun; Müller, Martin C.; Weiss, Christel; Duesberg, Peter; Hehlmann, Rüdiger; Hochhaus, Andreas; Seifarth, Wolfgang
- Abstract
Centrosomes play fundamental roles in mitotic spindle organisation, chromosome segregation and maintenance of genetic stability. Recently, we have demonstrated that the tyrosine kinase inhibitor imatinib induces centrosome and chromosome aberrations in vitro. Here, we comparatively investigated the effects of imatinib and the more potent successor drug nilotinib on centrosome, mitotic spindle and karyotype status in primary human fibroblasts. Therapeutic doses of imatinib and/or nilotinib administered separately, consecutively or in combination similarly induced centrosome, mitotic spindle, and karyotype aberrations. Our data suggest that distinct tyrosine kinases likewise targeted by both drugs are essential actuators in maintenance of centrosome and karyotype integrity.
- Subjects
CENTROSOMES; ANTINEOPLASTIC agents; PROTEIN-tyrosine kinase inhibitors; CHRONIC myeloid leukemia; CELL cycle; CHROMOSOME abnormalities
- Publication
British Journal of Haematology, 2007, Vol 138, Issue 3, p369
- ISSN
0007-1048
- Publication type
Article
- DOI
10.1111/j.1365-2141.2007.06678.x