التفاصيل البيبلوغرافية
| العنوان: |
Sensitivity of imatinib-resistant T315I BCR-ABL CML to a synergistic combination of ponatinib and forskolin treatment. |
| المؤلفون: |
Oaxaca, Derrick, Yang-Reid, Sun, Ross, Jeremy, Rodriguez, Georgialina, Staniswalis, Joan, Kirken, Robert |
| المصدر: |
Tumor Biology (Springer Science & Business Media B.V.); Sep2016, Vol. 37 Issue 9, p12643-12654, 12p |
| مستخلص: |
Tyrosine kinase inhibitors (TKIs) have dramatically improved the life expectancy of patients suffering from chronic myeloid leukemia (CML); however, patients will eventually develop resistance to TKI therapy or adverse side effects due to secondary off-target mechanisms associated with TKIs. CML patients exhibiting TKI resistance are at greater risk of developing an aggressive and drug-insensitive disease. Drug-resistant CML typically arises in response to spontaneous mutations within the drug binding sites of the targeted oncoproteins. To better understand the mechanism of drug resistance in TKI-resistant CML patients, the BCR-ABL transformed cell line KCL22 was grown with increasing concentrations of imatinib for a period of 6 weeks. Subsequently, a drug-resistant derivative of the parental KCL22 cell line harboring the T315I gatekeeper mutation was isolated and investigated for TKI drug sensitivity via multi-agent drug screens. A synergistic combination of ponatinib- and forskolin-reduced cell viability was identified in this clinically relevant imatinib-resistant CML cell line, which also proved efficacious in other CML cell lines. In summary, this study provides new insight into the biological underpinnings of BCR-ABL-driven CML and potential rationale for investigating novel treatment strategies for patients with T315I CML. [ABSTRACT FROM AUTHOR] |
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| قاعدة البيانات: |
Complementary Index |
