Linked Life Data

15990860

Source:http://linkedlifedata.com/resource/pubmed/id/15990860

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
9
pubmed:dateCreated
2005-8-24
pubmed:abstractText
Imatinib (STI571, Gleevec/Glivec) is a potent selective tyrosine kinase inhibitor and is used successfully in the treatment of chronic myeloid leukemia (CML). While karyotype alterations, in addition to the Philadelphia chromosome, are a common phenomenon of progressing CML, the observation of BCR-ABL-negative leukemic clones with distinct aberrant karyotypes under an imatinib regimen is not yet understood. Here we test the hypothesis that such tumor clones may be induced de novo from normal cells by imatinib. In vitro experiments with varying drug concentrations (5-20 microM) were performed on normal human dermal fibroblasts (NHDF), Chinese hamster embryonal and Indian muntjak fibroblasts. After 3 weeks of treatment, analysis of cell cultures by centrosome immunostaining and conventional cytogenetics revealed that imatinib induced centrosome and chromosome aberrations in all cultures in a significant dose-dependent and species-independent manner. Moreover, the results of NHDF long-term culture experiments demonstrated that aberrant phenotypes, emerging under imatinib treatment for 12 weeks, were not reversible after prolonged propagation omitting the drug. These observations suggest a causative role of imatinib in the origin of centrosome and karyotype aberrations (genetic instability) and thus may explain the emergence of clonal chromosomal abnormalities in BCR-ABL-negative progenitor cells under imatinib therapy.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Sep
pubmed:issn
0887-6924
pubmed:author
pubmed:issnType
Print
pubmed:volume
19
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
1573-8
pubmed:dateRevised
2006-11-15
pubmed:meshHeading
pubmed:year
2005
pubmed:articleTitle
Induction of centrosome and chromosome aberrations by imatinib in vitro.
pubmed:affiliation
III. Medizinische Universitätsklinik, Fakultät für Klinische Medizin Mannheim der Ruprecht-Karls-Universität Heidelberg, Mannheim, Germany. alice.fabarius@med3.ma.uni-heidelberg.de
pubmed:publicationType
Journal Article, In Vitro, Research Support, Non-U.S. Gov't