Results found: 3

Number of results on page

Search results

Sort By:

Limit search:

Reactive oxygen species in BCR-ABL1-expressing cells - relevance to chronic myeloid leukemia

100%

Antoszewska-Smith J., Pawlowska E., Blasiak J.

2017

vol. 64

issue 1

1-10

Chronic myeloid leukemia (CML) results from the t(9;22) reciprocal chromosomal translocation producing the BCR-ABL1 gene, conferring growth and proliferation advantages in the CML cells. CML progresses from chronic, often syndrome-free, to blast phase, fatal if not treated. Although the involvement of BCR-ABL1 in some signaling pathways is considered as the cause of CML, the mechanisms resulting in its progression are not completely known. However, BCR-ABL1 stimulates the production of reactive oxygen species (ROS), which levels increase with CML progression and induce BCR-ABL1 self-mutagenesis. Introducing imatinib and other tyrosine kinase inhibitors (TKIs) to CML therapy radically improved its outcome, but TKIs-resistance became an emerging problem. TKI resistance can be associated with even higher ROS production than in TKI-sensitive cells. Therefore, ROS-induced self-mutagenesis of BCR-ABL1 can be crucial for CML progression and TKI resistance and in this way should be taken into account in therapeutic strategies. As a continuous production of ROS by BCR-ABL1 would lead to its self-destruction and death of CML cells, there must be mechanisms controlling this phenomenon. These can be dependent on DNA repair, which is modulated by BCR-ABL1 and can be different in CML stem and progenitor cells. Altogether, the mechanisms of the involvement of BCR-ABL1 in ROS signaling can be engaged in CML progression and TKI-resistance and warrant further study.

Mitochondrial mutagenesis in BCR-ABL1-expressing cells sensitive and resistant to imatinib

88%

Blasiak J., Hoser G., Bialkowska-Warzecha J., Pawlowska E., Skorski T.

2016

vol. 63

issue 2

365-370

Imatinib revolutionized the treatment of chronic myeloid leukemia (CML) with the expression of the BCR-ABL1 tyrosine kinase, but imatinib resistance is an emerging problem. Imatinib can hinder the inhibitory effects of BCR-ABL1 on mitochondrial apoptotic pathway, so mitochondrial mutagenesis can be important for its action. To explore the mechanisms of imatinib resistance we created a mouse-derived CML model cells consisting of parental 32D cells (P) and cells transfected with the BCR-ABL1 gene (S cells) or its variants with the Y253H or T315I mutations (253 and 315 cells, respectively), conferring resistance to imatinib. A fraction of the S cells was cultured in increasing concentrations of imatinib, acquiring resistance to this drug (AR cells). The 253, 315 and AR cells, in contrast to S cells, displayed resistance to imatinib. We observed that the T315I cells displayed greater extent of H2O2-induced mtDNA damage than their imatinib-sensitive counterparts. No difference in the sensitivity to UV radiation was observed among all the cell lines. A decrease in the extent of H2O2-induced mtDNA damage was observed during a 120-min repair incubation in all cell lines, but it was significant only in imatinib-sensitive and T315I cells. No difference in the copy number of mtDNA and frequency of the 3,867-bp deletion was observed and genotoxic stress induced by H2O2 or UV did not change this relationship. In conclusion, some aspects of mtDNA mutagenesis, including sensitivity to oxidative stress and DNA repair can contribute to imatinib resistance in BCR-ABL1-expressing cells.

Transferrin receptor levels and polymorphism of its gene in age-related macular degeneration

64%

Wysokinski D., Danisz K., Pawlowska E., Dorecka M., Romaniuk D., Robaszkiewicz J., Szaflik M., Szaflik J., Blasiak J., Szaflik J.

2015

vol. 62

issue 2

177-184

The aim of the present study was to investigate the association of age related macular degeneration (AMD) risk with some aspects of iron homeostasis: iron concentration in serum, level of soluble transferrin receptor (sTfR), and transferrin receptor (TFRC) genetic variability. Four hundred and ninety one AMD patients and 171 controls were enrolled in the study. Restriction fragment length polymorphism PCR was employed to genotype polymorphisms of the TFRC gene, and colorimetric assays were used to determine the level of iron and sTfR. Multiple logistic regression was applied for all genotype/allele-related analyses and the ANOVA test for iron and sTfR serum level comparison. We found that the genotypes and alleles of the c.-253G > A polymorphism of the TFRC gene were associated with AMD risk and this association was modulated by smoking status, AMD family history, living environment (rural/urban), body mass index and age. The levels of sTfR was higher in AMD patients than controls, whereas concentrations of iron did not differ in these two groups. No association was found between AMD occurrence and the p.Gly142Ser polymorphism of the TRFC gene. The results obtained suggest that transferrin receptor and variability of its gene may influence AMD risk.

Refine search results

3 Acta Biochimica Polonica

1 2017

1 2016

1 2015

3 Blasiak J.

3 Pawlowska E.

1 Antoszewska-Smith J.

1 Bialkowska-Warzecha J.

1 Danisz K.

1 Dorecka M.

1 Hoser G.

1 Robaszkiewicz J.

1 Romaniuk D.

1 Skorski T.

1 Szaflik J.

1 Szaflik M.

1 Wysokinski D.

Search results

Reactive oxygen species in BCR-ABL1-expressing cells - relevance to chronic myeloid leukemia

Mitochondrial mutagenesis in BCR-ABL1-expressing cells sensitive and resistant to imatinib

Transferrin receptor levels and polymorphism of its gene in age-related macular degeneration