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Centrosome aberrations after nilotinib and imatinib treatment in vitro are associated with mitotic spindle defects and genetic instability
Author(s) -
Fabarius Alice,
Giehl Michelle,
Frank Oliver,
Spiess Birgit,
Zheng Chun,
Müller Martin C.,
Weiss Christel,
Duesberg Peter,
Hehlmann Rüdiger,
Hochhaus Andreas,
Seifarth Wolfgang
Publication year - 2007
Publication title -
british journal of haematology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.907
H-Index - 186
eISSN - 1365-2141
pISSN - 0007-1048
DOI - 10.1111/j.1365-2141.2007.06678.x
Subject(s) - centrosome , nilotinib , mitosis , biology , microbiology and biotechnology , imatinib , cancer research , spindle apparatus , multipolar spindles , genetics , cell cycle , cell division , cell , myeloid leukemia
Summary 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.