5 research outputs found

    Bcr/Abl Interferes with the Fanconi Anemia/BRCA Pathway: Implications in the Chromosomal Instability of Chronic Myeloid Leukemia Cells

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    Chronic myeloid leukemia (CML) is a malignant clonal disorder of the hematopoietic system caused by the expression of the BCR/ABL fusion oncogene. Although it is well known that CML cells are genetically unstable, the mechanisms accounting for this genomic instability are still poorly understood. Because the Fanconi anemia (FA) pathway is believed to control several mechanisms of DNA repair, we investigated whether this pathway was disrupted in CML cells. Our data show that CML cells have a defective capacity to generate FANCD2 nuclear foci, either in dividing cells or after DNA damage. Similarly, human cord blood CD34+ cells transduced with BCR/ABL retroviral vectors showed impaired FANCD2 foci formation, whereas FANCD2 monoubiquitination in these cells was unaffected. Soon after the transduction of CD34+ cells with BCR/ABL retroviral vectors a high proportion of cells with supernumerary centrosomes was observed. Similarly, BCR/ABL induced a high proportion of chromosomal abnormalities, while mediated a cell survival advantage after exposure to DNA cross-linking agents. Significantly, both the impaired formation of FANCD2 nuclear foci, and also the predisposition of BCR/ABL cells to develop centrosomal and chromosomal aberrations were reverted by the ectopic expression of BRCA1. Taken together, our data show for the first time a disruption of the FA/BRCA pathway in BCR/ABL cells, suggesting that this defective pathway should play an important role in the genomic instability of CML by the co-occurrence of centrosomal amplification and DNA repair deficiencies

    Earlinet instrument intercomparison campaigns: overview on strategy and results

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    This paper introduces the recent European Aerosol Research Lidar Network (EARLINET) quality-assurance efforts at instrument level. Within two dedicated campaigns and five single-site intercomparison activities, 21 EARLINET systems from 18 EARLINET stations were intercompared between 2009 and 2013. A comprehensive strategy for campaign setup and data evaluation has been established. Eleven systems from nine EARLINET stations participated in the EARLINET Lidar Intercomparison 2009 (EARLI09). In this campaign, three reference systems were qualified which served as traveling standards thereafter. EARLINET systems from nine other stations have been compared against these reference systems since 2009. We present and discuss comparisons at signal and at product level from all campaigns for more than 100 individual measurement channels at the wavelengths of 355, 387, 532, and 607 nm. It is shown that in most cases, a very good agreement of the compared systems with the respective reference is obtained. Mean signal deviations in predefined height ranges are typically below +/- 2 %. Particle backscatter and extinction coefficients agree within +/- 2 x 10(-4) km(-1) sr(-1) and +/- 0.01 km(-1), respectively, in most cases. For systems or channels that showed larger discrepancies, an in-depth analysis of deficiencies was performed and technical solutions and upgrades were proposed and realized. The intercomparisons have reinforced confidence in the EARLINET data quality and allowed us to draw conclusions on necessary system improvements for some instruments and to identify major challenges that need to be tackled in the future
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