Contributions
Abstract: PB1808
Type: Publication Only
Background
Therapies targeting the redox environment such as over-expression of antioxidants or antioxidant treatment, could inhibit tumor cell growth even resistant cells. Bcr-Abl oncogene is known to induce high levels of intracellular ROS which may further induce genomic instability with malignant transformation and even imatinib (IM) resistance. Variable expression of antioxidants enzymes in leukemia, with limited studies with variable results so far. Altered redox biology in leukemia also has implications for therapeutics.
Aims
We investigated the roles of PRX II in CML primary cells at diagnosis and remission during signal transduction inhibitor (STIs), and tested the same roles in Ph+ cell lines.
Methods
Three BCR-ABL1 positive cell lines with different resistance to TKI and generating IM-resistant K562 cells by chronic exposure of increasing concentrations of IM were compared with cell growth by MTT assay, BCR/ABL expression by western blot analysis, changes of intracellular ROS level and antioxidant enzymes such as peroxiredoxin (Prx) 1, 2, 3 using immunoblot assay according to different concentrations of IM between 0 to 10 μM in time dependent manner (24 hours/48 hours). We also repeatedly investigated the effects of IM therapy using PRXII overexpressed K562 cells by transfection.
Results
Three BCR-ABL1 positive cell lines showed significant change in cell viability, Intracellular ROS level, eradication of BCR/ABL oncogene and levels of Prx2 during IM treatment with different response each other in degree and pattern by IM exposure. The levels of BCR-ABL1 oncogene were slightly decreased in Prx2 overexpressed K562 cells. Moreover, Prx2 overexpressed K562 cells showed further down-regulation of Bcr-Abl oncoprotein by IM treatment.
Conclusion
Session topic: 7. Chronic myeloid leukemia - Biology
Keyword(s): Ph chromosome, imatinib, Chronic myeloid leukemia, Reactive oxygen species
Abstract: PB1808
Type: Publication Only
Background
Therapies targeting the redox environment such as over-expression of antioxidants or antioxidant treatment, could inhibit tumor cell growth even resistant cells. Bcr-Abl oncogene is known to induce high levels of intracellular ROS which may further induce genomic instability with malignant transformation and even imatinib (IM) resistance. Variable expression of antioxidants enzymes in leukemia, with limited studies with variable results so far. Altered redox biology in leukemia also has implications for therapeutics.
Aims
We investigated the roles of PRX II in CML primary cells at diagnosis and remission during signal transduction inhibitor (STIs), and tested the same roles in Ph+ cell lines.
Methods
Three BCR-ABL1 positive cell lines with different resistance to TKI and generating IM-resistant K562 cells by chronic exposure of increasing concentrations of IM were compared with cell growth by MTT assay, BCR/ABL expression by western blot analysis, changes of intracellular ROS level and antioxidant enzymes such as peroxiredoxin (Prx) 1, 2, 3 using immunoblot assay according to different concentrations of IM between 0 to 10 μM in time dependent manner (24 hours/48 hours). We also repeatedly investigated the effects of IM therapy using PRXII overexpressed K562 cells by transfection.
Results
Three BCR-ABL1 positive cell lines showed significant change in cell viability, Intracellular ROS level, eradication of BCR/ABL oncogene and levels of Prx2 during IM treatment with different response each other in degree and pattern by IM exposure. The levels of BCR-ABL1 oncogene were slightly decreased in Prx2 overexpressed K562 cells. Moreover, Prx2 overexpressed K562 cells showed further down-regulation of Bcr-Abl oncoprotein by IM treatment.
Conclusion
Session topic: 7. Chronic myeloid leukemia - Biology
Keyword(s): Ph chromosome, imatinib, Chronic myeloid leukemia, Reactive oxygen species