Characterization of imatinib-resistant K562 cell line displaying resistance mechanisms.

Characterization of imatinib-resistant K562 cell line displaying resistance mechanisms. Cell Mol Biol (Noisy-le-grand). 2018 May 15;64(6):23-30 Authors: Hekmatshoar Y, Ozkan T, Altinok Gunes B, Bozkurt S, Karadag A, Karabay AZ, Sunguroglu A Abstract Chronic myeloid leukemia (CML) is a hematopoietic malignancy characterized by the t(9; 22) and the related oncogene, BCR-ABL. Tyrosine kinase activity of fusion protein BCR-ABL is the main cause of CML. Even if imatinib is used as a tyrosine kinase inhibitor (TKI) for CML therapy, drug resistance may occur in patients and the clinical failure of imatinib treatment in resistant patients had resulted with the use of another alternative TKIs. BCR-ABL dependent and independent molecular mechanisms have crucial roles in drug resistance. To reveal the underlying molecular mechanisms which play significant roles in imatinib resistance in CML, we established K562 imatinib-resistant cell line (K562r5) which was continuously exposed to (5µM) imatinib to investigate molecular mechanisms which play significant roles in drug resistance. First of all, we analyzed T315I, M351T, F315L and F359C/L/V mutations with DNA sequencing as a BCR-ABL dependent mechanism in our cell lines. Moreover, we investigated BCR-ABL independent mechanisms such as apoptosis, autophagy, drug transport and DNA repair which affect drug resistance in these cell lines. In vitro cell viability was determined by MTT assay. DNA sequ...
Source: Cellular and Molecular Biology - Category: Molecular Biology Tags: Cell Mol Biol (Noisy-le-grand) Source Type: research