Semi-random mutagenesis profile of BCR-ABL during imatinib resistance acquirement in K562 cells

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Semi-random mutagenesis profile of BCR-ABL during imatinib resistance acquirement in K562 cells

Although imatinib is effective in chronic myeloid leukemia treatment, imatinib resistance due to the T315I mutation and/or other mutations is a challenge to be overcome. However, how DNA mutation occurs, particularly the T315I mutation, remains unclear. In the current study, the mutagenesis of BCR‑ABL was analyzed via focusing on the process of drug resistance, rather than the final results. Cl...

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Evaluation of the Effect of Curcumin and Imatinib on BCR-ABL Expression Gene in Chronic Human k562 Cells

Background and Aims: Detection of overexpression in tumor-inhibiting genes provides valuable information for leukemia diagnosis and prognosis. Chronic myeloid leukemia (CML) is a stem cell disorder determined by a well-defined genetic anomaly involving BCR-ABL translocation in the Philadelphia chromosome. Curcumin is a chemo-preventive agent for the primary cancer targets, such as the breast, p...

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Resistance to imatinib of bcr/abl p190 lymphoblastic leukemia cells.

Around 20% of patients with acute lymphoblastic leukemia are Philadelphia chromosome positive (Ph-positive acute lymphoblastic leukemia) and express the Bcr/Abl tyrosine kinase. Treatment with the tyrosine kinase inhibitor Imatinib is currently standard for chronic myelogenous leukemia, which is also caused by Bcr/Abl. However, Imatinib has shown limited efficacy for treating Ph-positive acute ...

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Mechanisms of Autoinhibition and STI-571/Imatinib Resistance Revealed by Mutagenesis of BCR-ABL

The Bcr-Abl fusion protein kinase causes chronic myeloid leukemia and is targeted by the signal transduction inhibitor STI-571/Gleevec/imatinib (STI-571). Sequencing of the BCR-ABL gene in patients who have relapsed after STI-571 chemotherapy has revealed a limited set of kinase domain mutations that mediate drug resistance. To obtain a more comprehensive survey of the amino acid substitutions ...

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BCR/ABL kinase induces self-mutagenesis via reactive oxygen species to encode imatinib resistance.

Mutations in the BCR/ABL kinase domain play a major role in resistance to imatinib mesylate (IM). We report here that BCR/ABL kinase stimulates reactive oxygen species (ROS), which causes oxidative DNA damage, resulting in mutations in the kinase domain. The majority of mutations involved A/T-->G/C and G/C-->A/T transitions, a phenotype detected previously in patients, which encoded clinically ...

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ژورنال

عنوان ژورنال: Molecular Medicine Reports

سال: 2017

ISSN: 1791-2997,1791-3004

DOI: 10.3892/mmr.2017.7835