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Superoxide AND tyron

Margaret Nieborowska-Skorska, Piotr K Kopinski, Regina Ray, Grazyna Hoser, Danielle Ngaba, Sylwia Flis, Kimberly Cramer, Mamatha M Reddy, Mateusz Koptyra, Tyrone Penserga, Eliza Glodkowska-Mrowka, Elisabeth Bolton, Tessa L Holyoake, Connie J Eaves, Sabine Cerny-Reiterer, Peter Valent, Andreas Hochhaus, Timothy P Hughes, Heiko van der Kuip, Martin Sattler, Wieslaw Wiktor-Jedrzejczak, Christine Richardson, Adrienne Dorrance, Tomasz Stoklosa, David A Williams, Tomasz Skorski
Chronic myeloid leukemia in chronic phase (CML-CP) is induced by BCR-ABL1 oncogenic tyrosine kinase. Tyrosine kinase inhibitors eliminate the bulk of CML-CP cells, but fail to eradicate leukemia stem cells (LSCs) and leukemia progenitor cells (LPCs) displaying innate and acquired resistance, respectively. These cells may accumulate genomic instability, leading to disease relapse and/or malignant progression to a fatal blast phase. In the present study, we show that Rac2 GTPase alters mitochondrial membrane potential and electron flow through the mitochondrial respiratory chain complex III (MRC-cIII), thereby generating high levels of reactive oxygen species (ROS) in CML-CP LSCs and primitive LPCs...
May 3, 2012: Blood
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