Year

2006

Type(s)

Journal Article

Author(s)

Majsterek, Ireneusz and Sliwinski, Tomasz and Poplawski, Tomasz and Pytel, Dariusz and Kowalski, Michal and Slupianek, Artur and Skorski, Tomasz and Blasiak, Janusz

Source

Mutation Research/Genetic Toxicology and Environmental Mutagenesis, 603(1): 74—82, 2006

Url

http://www.sciencedirect.com/science/article/pii/S138357180500286X

BibTeX

BibTeX

BibTeX

@article{majsterek_imatinib_2006, title = {Imatinib mesylate ({STI}571) abrogates the resistance to doxorubicin in human {K}562 chronic myeloid leukemia cells by inhibition of {BCR}/{ABL} kinase-mediated {DNA} repair}, volume = {603}, issn = {1383-5718}, url = {http://www.sciencedirect.com/science/article/pii/S138357180500286X}, doi = {10.1016/j.mrgentox.2005.10.010}, abstract = {Imatinib mesylate (STI571), a specific inhibitor of BCR/ABL tyrosine kinase, exhibits potent antileukemic effects in the treatment of chronic myelogenous leukemia (CML). However, the precise mechanism by which inhibition of BCR/ABL activity results in pharmacological responses remains unknown. BCR/ABL-positive human K562 CML cells resistant to doxorubicin (K562DoxR) and their sensitive counterparts (K562DoxS) were used to determine the mechanism by which the STI571 inhibitor may overcome drug resistance. K562 wild type cells and CCRF-CEM lymphoblastic leukemia cells without BCR/ABL were used as controls. The STI571 specificity was examined by use of murine pro-B lymphoid Baf3 cells with or without BCR/ABL kinase expression. We examined kinetics of DNA repair after cell treatment with doxorubicin in the presence or absence of STI571 by the alkaline comet assay. The MTT assay was used to estimate resistance against doxorubicin and Western blot analysis with Crk-L antibody was performed to evaluate BCR/ABL kinase inhibition by STI571. We provide evidence that treatment of CML-derived BCR/ABL-expressing leukemia K562 cells with STI571 results in the inhibition of DNA repair and abrogation of the resistance of these cells to doxorubicin. We found that doxorubicin-resistant K562DoxR cells exhibited accelerated kinetics of DNA repair compared with doxorubicin-sensitive K562DoxS cells. Inhibition of BCR/ABL kinase in K562DoxR cells with 1 μM STI571 decreased the kinetics of DNA repair and abrogated drug resistance. The results suggest that STI571-mediated inhibition of BCR/ABL kinase activity can affect the effectiveness of the DNA-repair pathways, which in turn may enhance drug sensitivity of leukemia cells.}, number = {1}, urldate = {2014-11-03}, journal = {Mutation Research/Genetic Toxicology and Environmental Mutagenesis}, author = {Majsterek, Ireneusz and Sliwinski, Tomasz and Poplawski, Tomasz and Pytel, Dariusz and Kowalski, Michal and Slupianek, Artur and Skorski, Tomasz and Blasiak, Janusz}, month = jan, year = {2006}, keywords = {DNA Repair, bcr/abl, drug resistance, Leukemia, sti571}, pages = {74--82}, file = {ScienceDirect Full Text PDF:C:\Users\Tomasz Poplawski\Zotero\storage\75A6BSNA\Majsterek i in. - 2006 - Imatinib mesylate (STI571) abrogates the resistanc.pdf:application/pdf;ScienceDirect Snapshot:C:\Users\Tomasz Poplawski\Zotero\storage\J4KNXIFK\S138357180500286X.html:text/html}