| 11. |
- Andersson, Anna, et al.
(author)
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The landscape of somatic mutations in infant MLL-rearranged acute lymphoblastic leukemias.
- 2015
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In: Nature Genetics. - : Springer Science and Business Media LLC. - 1546-1718 .- 1061-4036. ; 47:4, s. 192-330
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Journal article (peer-reviewed)abstract
- Infant acute lymphoblastic leukemia (ALL) with MLL rearrangements (MLL-R) represents a distinct leukemia with a poor prognosis. To define its mutational landscape, we performed whole-genome, exome, RNA and targeted DNA sequencing on 65 infants (47 MLL-R and 18 non-MLL-R cases) and 20 older children (MLL-R cases) with leukemia. Our data show that infant MLL-R ALL has one of the lowest frequencies of somatic mutations of any sequenced cancer, with the predominant leukemic clone carrying a mean of 1.3 non-silent mutations. Despite this paucity of mutations, we detected activating mutations in kinase-PI3K-RAS signaling pathway components in 47% of cases. Surprisingly, these mutations were often subclonal and were frequently lost at relapse. In contrast to infant cases, MLL-R leukemia in older children had more somatic mutations (mean of 6.5 mutations/case versus 1.3 mutations/case, P = 7.15 × 10(-5)) and had frequent mutations (45%) in epigenetic regulators, a category of genes that, with the exception of MLL, was rarely mutated in infant MLL-R ALL.
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| 12. |
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| 13. |
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| 14. |
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| 15. |
- Faber, Zachary J, et al.
(author)
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The genomic landscape of core-binding factor acute myeloid leukemias
- 2016
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In: Nature Genetics. - : Springer Science and Business Media LLC. - 1546-1718 .- 1061-4036. ; 48, s. 1551-1556
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Journal article (peer-reviewed)abstract
- Acute myeloid leukemia (AML) comprises a heterogeneous group of leukemias frequently defined by recurrent cytogenetic abnormalities, including rearrangements involving the core-binding factor (CBF) transcriptional complex. To better understand the genomic landscape of CBF-AMLs, we analyzed both pediatric (n = 87) and adult (n = 78) samples, including cases with RUNX1-RUNX1T1 (n = 85) or CBFB-MYH11 (n = 80) rearrangements, by whole-genome or whole-exome sequencing. In addition to known mutations in the Ras pathway, we identified recurrent stabilizing mutations in CCND2, suggesting a previously unappreciated cooperating pathway in CBF-AML. Outside of signaling alterations, RUNX1-RUNX1T1 and CBFB-MYH11 AMLs demonstrated remarkably different spectra of cooperating mutations, as RUNX1-RUNX1T1 cases harbored recurrent mutations in DHX15 and ZBTB7A, as well as an enrichment of mutations in epigenetic regulators, including ASXL2 and the cohesin complex. This detailed analysis provides insights into the pathogenesis and development of CBF-AML, while highlighting dramatic differences in the landscapes of cooperating mutations for these related AML subtypes.
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| 16. |
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| 17. |
- Hua, Sha, et al.
(author)
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Influence of APOA5 locus on the treatment efficacy of three statins : Evidence from a randomized pilot study in Chinese subjects
- 2018
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In: Frontiers in Pharmacology. - : Frontiers Media SA. - 1663-9812. ; 9:APR
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Journal article (peer-reviewed)abstract
- Pharmacogenetics or pharmacogenomics approaches are important for addressing the individual variabilities of drug efficacy especially in the era of precision medicine. One particular interesting gene to investigate is APOA5, which has been repeatedly linked with the inter-individual variations of serum triglycerides. Here, we explored APOA5-statin interactions in 195 Chinese subjects randomized to rosuvastatin (5-10 mg/day), atorvastatin (10-20 mg/day), or simvastatin (40 mg/day) for 12 weeks by performing a targeted genotyping analysis of the APOA5 promoter SNP rs662799 (-1131T > C). There were no significant differences between the treatment arms for any of the statin-induced changes in clinical biomarkers. Reductions in LDL cholesterol were influenced by the APOA5 genotype in all three treatment groups. By contrast, changes in HDL cholesterol, and triglycerides were only affected by the APOA5 genotype in the atorvastatin and simvastatin groups and not in the rosuvastatin group. Our results suggest that future studies may need to consider stratifying subjects not only by genetic background but also by prescribed statin type.
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| 18. |
- Hyrenius-Wittsten, Axel, et al.
(author)
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De novo activating mutations drive clonal evolution and enhance clonal fitness in KMT2A-rearranged leukemia
- 2018
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In: Nature Communications. - : Springer Science and Business Media LLC. - 2041-1723. ; 9:1
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Journal article (peer-reviewed)abstract
- Activating signaling mutations are common in acute leukemia with KMT2A (previously MLL) rearrangements (KMT2A-R). These mutations are often subclonal and their biological impact remains unclear. Using a retroviral acute myeloid mouse leukemia model, we demonstrate that FLT3 ITD, FLT3 N676K, and NRAS G12D accelerate KMT2A-MLLT3 leukemia onset. Further, also subclonal FLT3 N676K mutations accelerate disease, possibly by providing stimulatory factors. Herein, we show that one such factor, MIF, promotes survival of mouse KMT2A-MLLT3 leukemia initiating cells. We identify acquired de novo mutations in Braf, Cbl, Kras, and Ptpn11 in KMT2A-MLLT3 leukemia cells that favored clonal expansion. During clonal evolution, we observe serial genetic changes at the Kras G12D locus, consistent with a strong selective advantage of additional Kras G12D . KMT2A-MLLT3 leukemias with signaling mutations enforce Myc and Myb transcriptional modules. Our results provide new insight into the biology of KMT2A-R leukemia with subclonal signaling mutations and highlight the importance of activated signaling as a contributing driver.
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| 19. |
- Jin, Jing, et al.
(author)
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Fabrication of a polypropylene immunoassay platform by photografting reaction
- 2019
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In: Materials science & engineering. C, biomimetic materials, sensors and systems. - : ELSEVIER SCIENCE BV. - 0928-4931 .- 1873-0191. ; 102, s. 492-501
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Journal article (peer-reviewed)abstract
- The technology of an immunoassay detection platform is critical to clinical disease diagnoses, especially for developing a medical diagnostic system. A polymer-based immunoassay platform was fabricated on nonwoven fabric polypropylene (PP) using a photografting reaction to graft 2-hydroxyethyl methacrylate (HEMA) and sulfobetaine (SBMA). The antifouling properties of PP-g-P(HEMA-co-SBMA) were investigated by fibrinogen adsorption and platelet adhesion. Carbonyldiimidazole was employed to activate the pendant hydroxyl groups in HEMA moieties and covalently coupled antibody molecules. The detection of the limit of the immunoassay platform was as low as 10 pg/mL. Antibody amount and bioactivity affected the availability of antibody and the sensitivity of immunoassay. The immune efficiency was dependent on the strategies of antibody immobilization. The immune efficiency of Au-g-P(SBMA-co-HEMA) and Au-SH surfaces measured by QCM-D was 165% and 35.7%, respectively. The covalently binding antibody via hydrophilic polymer chains as spacers could retain fragment antigen-binding up orientation, maintain the bioactivity of antibody, and mainly improve the accessibility of antibody molecules via adjusting the conformations of polymer chains when the antibodies recognized the antigens. Therefore, grafting hydrophilic polymers, such as zwitterionic PSBMA and reactive PHEMA onto nonwoven fabric PP, and binding antibody by covalent strategy had the potential to be developed as a commercial immunoassay platform.
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| 20. |
- Kristanl, Matej, et al.
(author)
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The Seventh Visual Object Tracking VOT2019 Challenge Results
- 2019
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In: 2019 IEEE/CVF INTERNATIONAL CONFERENCE ON COMPUTER VISION WORKSHOPS (ICCVW). - : IEEE COMPUTER SOC. - 9781728150239 ; , s. 2206-2241
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Conference paper (peer-reviewed)abstract
- The Visual Object Tracking challenge VOT2019 is the seventh annual tracker benchmarking activity organized by the VOT initiative. Results of 81 trackers are presented; many are state-of-the-art trackers published at major computer vision conferences or in journals in the recent years. The evaluation included the standard VOT and other popular methodologies for short-term tracking analysis as well as the standard VOT methodology for long-term tracking analysis. The VOT2019 challenge was composed of five challenges focusing on different tracking domains: (i) VOT-ST2019 challenge focused on short-term tracking in RGB, (ii) VOT-RT2019 challenge focused on "real-time" short-term tracking in RGB, (iii) VOT-LT2019 focused on long-term tracking namely coping with target disappearance and reappearance. Two new challenges have been introduced: (iv) VOT-RGBT2019 challenge focused on short-term tracking in RGB and thermal imagery and (v) VOT-RGBD2019 challenge focused on long-term tracking in RGB and depth imagery. The VOT-ST2019, VOT-RT2019 and VOT-LT2019 datasets were refreshed while new datasets were introduced for VOT-RGBT2019 and VOT-RGBD2019. The VOT toolkit has been updated to support both standard short-term, long-term tracking and tracking with multi-channel imagery. Performance of the tested trackers typically by far exceeds standard baselines. The source code for most of the trackers is publicly available from the VOT page. The dataset, the evaluation kit and the results are publicly available at the challenge website(1).
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