Abstract | OBJECTIVES:
Tyrosine kinase inhibitors (TKIs) target various pathways associated with proliferation of aberrant clones in malignant diseases. Despite good response and acceptable tolerability, little is known concerning long-term toxicity. Furthermore, the influence of these inhibitors on disease-unrelated cells is not investigated yet. METHODS: RESULTS: OM cells (n = 12) and fibroblasts (n = 7) of patients with CML treated with dasatinib and OM cells of three patients with CML treated with bosutinib showed centrosomal alterations (mean, 14%) compared with 16 (10 OM and 6 fibroblasts) controls (mean, 3%). OM cells of five patients with CML and one patient with systemic mastocytosis treated with imatinib or nilotinib and of eight patients with RCC or HCC treated with sorafenib or sunitinib showed centrosome defects in a mean of 15%. CONCLUSIONS: Our data have shown that TKI treatment of tumor patients may influence centrosomes in disease-unrelated cells or tissues. This may be important with regard to various observed side effects.
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Authors | Michelle Giehl, Armin Leitner, Claudia Haferlach, Peter Duesberg, Wolf-Karsten Hofmann, Ralf Hofheinz, Wolfgang Seifarth, Andreas Hochhaus, Alice Fabarius |
Journal | European journal of haematology
(Eur J Haematol)
Vol. 85
Issue 2
Pg. 139-48
(Aug 2010)
ISSN: 1600-0609 [Electronic] England |
PMID | 20408871
(Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
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Chemical References |
- Aniline Compounds
- Nitriles
- Protein Kinase Inhibitors
- Pyrimidines
- Quinolines
- Thiazoles
- bosutinib
- Dasatinib
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Topics |
- Adult
- Aged
- Aniline Compounds
(adverse effects, therapeutic use, toxicity)
- Case-Control Studies
- Centrosome
(drug effects, pathology)
- Dasatinib
- Female
- Fibroblasts
(drug effects)
- Humans
- Leukemia, Myelogenous, Chronic, BCR-ABL Positive
(drug therapy)
- Male
- Middle Aged
- Mouth Mucosa
(drug effects)
- Nitriles
(adverse effects, therapeutic use, toxicity)
- Protein Kinase Inhibitors
(adverse effects, therapeutic use, toxicity)
- Pyrimidines
(adverse effects, therapeutic use, toxicity)
- Quinolines
(adverse effects, therapeutic use, toxicity)
- Thiazoles
(adverse effects, therapeutic use, toxicity)
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