TEL-fusion oncogenic tyrosine kinases determine leukemic cells response to idarubicin
作者:
Ireneusz Majsterek,
Artur Slupianek,
Janusz Blasiak,
期刊:
Anti-Cancer Drugs
(OVID Available online 2003)
卷期:
Volume 14,
issue 8
页码: 625-631
ISSN:0959-4973
年代: 2003
出版商: OVID
关键词: Comet assay;DNA repair;drug resistance;fusion tyrosine kinase;leukemia;MTT;idarubicin;TEL/ABL;TEL/JAK2;TEL/PDGF&bgr;R
数据来源: OVID
摘要:
The family of BCR/ABL-related fusion tyrosine kinases (FTKs) is reported to participate in drug resistance in leukemogenesis. Our recent studies revealed a novel potential mechanism of resistance inFTK+cells underlined by the stimulation of DNA repair. In this work we examined a role of TEL family fusion oncoproteins in the response to idarubicin. We used murine pro-B lymphoid cell line BaF3, and itsTEL/ABL,TEL/JAK2andTEL/PDGF&bgr;R-transformed clones. The transformed cells, in contrast to their non-transformed counterparts, exhibited resistance to idarubicin in the range 0.01–1 μM. The drug at 0.3 and 1 μM induced DNA damage in the form of strand breaks or/and alkali-labile sites in both transformed and control cells as evaluated by the alkaline Comet assay. The transformed cells removed the damage within 60 min, while the control cells required 120 min to recover. The results obtained suggest that TEL-related FTKs may stimulate the repair of DNA damaged by idarubicin and be relevant to the resistance of the leukemic cells to this drug.
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