Whole Exome Sequencing of Chronic Myeloid Leukemia Patients.

BACKGROUND: Previous studies have shown that leukemogenic chromosomal translocations, including fusions between Break point Cluster Region (BCR) and Abelson (ABL) are present in the peripheral blood of healthy individuals. The aim of this study was to gain insights into the genetic alterations other than BCR-Abl translocation in molecular level, which cause chronic myeloid leukemia (CML). METHODS: We performed whole-exome sequencing on four cases representative of BCR-ABL positive CML in chronic phase of the disease. RESULTS: We did not identify any pathogenic mutation in all known genes involved in CML or other cancers in our subjects. Nevertheless, we identified polymorphisms in related genes. CONCLUSION: It is the first report of exome sequencing in Philadelphia chromosome positive CML patients. We did not identify any pathogenic mutation in known cancer genes in our patients who can be due to CML pathogenesis or technical limitations.

Generation of stable ARE- driven reporter system for monitoring oxidative stress.

BACKGROUND: NF-E2-related factor2 (Nrf2)-antioxidant response element (ARE) signaling pathway is the major defensive mechanism against oxidative stress and is up regulated by specific antioxidants and oxidants to comprise the chemoptotective response. Detection of ARE-activating compounds helps to develop new drugs and identify/quantify the tension range of the oxidants. Important reasons promoting this work are high throughput, rapid and inexpensive experiments relative to the in vitro studies for ARE-Nrf2 pathway monitoring of chemicals and environmental samples. METHODS: In this study hepatoma Huh7 reporter cell line was generated which contains a luciferase gene under the control of an ARE. This is the first example of ARE construct containing one copy of extended consensus response element. The cells were treated with hydroquinone (HQ) and p-benzoquinone (BQ) (oxidative stress inducers) and the antioxidant, curcumin. RESULTS: The luciferase activity was induced in a concentration-dependent manner in a concentration range of 1-2 µM for BQ and HQ. Curcumin was also validated as an ARE inducer in concentration above 10 µM. In addition, this reporter cell line provides a rapid detection as early as 4 h to respond to the ARE inducers. CONCLUSION: It is a powerful tool for the sensitive and selective screening of chemicals, drugs and environmental samples for their antioxidant and oxidant activities.