title: Centrosome aberrations after nilotinib and imatinib treatment in vitro are associated with mitotic spindle defects and genetic instability.
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.
authors.affiliation: III. Medizinische Universitätsklinik, Medizinische Fakultät Mannheim der Universität Heidelberg, Mannheim, Germany. alice.fabarius@med3.ma.uni-heidelberg.de
authors.forename: Alice
authors.initials: A
authors.lastname: Fabarius
authors.forename: Michelle
authors.initials: M
authors.lastname: Giehl
authors.forename: Oliver
authors.initials: O
authors.lastname: Frank
authors.forename: Birgit
authors.initials: B
authors.lastname: Spiess
authors.forename: Chun
authors.initials: C
authors.lastname: Zheng
authors.forename: Martin C
authors.initials: MC
authors.lastname: Müller
authors.forename: Christel
authors.initials: C
authors.lastname: Weiss
authors.forename: Peter
authors.initials: P
authors.lastname: Duesberg
authors.forename: Rüdiger
authors.initials: R
authors.lastname: Hehlmann
authors.forename: Andreas
authors.initials: A
authors.lastname: Hochhaus
authors.forename: Wolfgang
authors.initials: W
authors.lastname: Seifarth
mesh_terms: D000704:Analysis of Variance; D000970:Antineoplastic Agents / Q000009:adverse effects*; D001549:Benzamides; D002478:Cells, Cultured; D018385:Centrosome / Q000648:ultrastructure*; D043171:Chromosomal Instability; D002869:Chromosome Aberrations / Q000139:chemically induced*; D005347:Fibroblasts / Q000648:ultrastructure; D006801:Humans; D000068877:Imatinib Mesylate; D007621:Karyotyping; D010879:Piperazines / Q000009:adverse effects*; D011743:Pyrimidines / Q000009:adverse effects*; D012044:Regression Analysis; D008941:Spindle Apparatus / Q000648:ultrastructure*
chemical_list: D000970:Antineoplastic Agents; D001549:Benzamides; D010879:Piperazines; D011743:Pyrimidines; D000068877:Imatinib Mesylate; C498826:nilotinib