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  • 1
    Publication Date: 2016-12-09
    Description: Blastic plasmacytoid dendritic cell (PDC) neoplasm (BPDCN) is an aggressive hematological malignancy with a poor prognosis that derives from PDCs. No consensus for optimal treatment modalities is available today and the full characterization of this leukemia is still emerging. We identified here a BPDCN-specific transcriptomic profile when compared with those of acute myeloid leukemia and T-acute lymphoblastic leukemia, as well as the transcriptomic signature of primary PDCs. This BPDCN gene signature identified a dysregulation of genes involved in cholesterol homeostasis, some of them being liver X receptor (LXR) target genes. LXR agonist treatment of primary BPDCN cells and BPDCN cell lines restored LXR target gene expression and increased cholesterol efflux via the upregulation of adenosine triphosphate–binding cassette (ABC) transporters, ABCA1 and ABCG1. LXR agonist treatment was responsible for limiting BPDCN cell proliferation and inducing intrinsic apoptotic cell death. LXR activation in BPDCN cells was shown to interfere with 3 signaling pathways associated with leukemic cell survival, namely: NF-B activation, as well as Akt and STAT5 phosphorylation in response to the BPDCN growth/survival factor interleukin-3. These effects were increased by the stimulation of cholesterol efflux through a lipid acceptor, the apolipoprotein A1. In vivo experiments using a mouse model of BPDCN cell xenograft revealed a decrease of leukemic cell infiltration and BPDCN-induced cytopenia associated with increased survival after LXR agonist treatment. This demonstrates that cholesterol homeostasis is modified in BPDCN and can be normalized by treatment with LXR agonists which can be proposed as a new therapeutic approach.
    Keywords: Myeloid Neoplasia
    Print ISSN: 0006-4971
    Electronic ISSN: 1528-0020
    Topics: Biology , Medicine
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  • 2
    Publication Date: 2012-09-20
    Description: Purpose: To compare pure molecular diffusion, D , perfusion-related diffusion, D *, and perfusion fraction, f , determined from diffusion-weighted (DW) magnetic resonance (MR) imaging on the basis of the intravoxel incoherent motion (IVIM) theory in patients with type 2 diabetes with and without liver steatosis. Materials and Methods: This prospective study was approved by the appropriate ethics committee, and written informed consent was obtained from all patients. Between December 2009 and September 2011, 108 patients with type 2 diabetes (51 men, 57 women; mean age, 50 years) underwent 3.0-T single-voxel point-resolved proton MR spectroscopy of the liver (segment VII) to calculate the liver fat fraction from water (4.76 ppm) and methylene (1.33 ppm) peaks, corrected for T1 and T2 decay. Steatosis was defined as a liver fat fraction of at least 5.56%. DW imaging was performed by using a single-shot echo-planar sequence with 11 b values (0, 5, 15, 25, 35, 50, 100, 200, 400, 600, 800 sec/mm 2 ). Liver D , D *, and f were measured and compared in patients with and patients without steatosis (Mann-Whitney test). Results: The mean liver fat fraction was 7.8% (standard deviation, 9%; range, 0.99%–45%). Forty patients had liver steatosis. D was significantly lower in steatotic compared with nonsteatotic livers (mean, 1.03 x 10 –3 mm 2 /sec ± 0.23 [standard deviation] vs 1.24 x 10 –3 mm 2 /sec ± 0.15, respectively; P 〈 .0001), as was D * (mean, 72.2 x 10 –3 mm 2 /sec ± 61.4 vs 110.6 x 10 –3 mm 2 /sec ± 79; P = .0025). However, f was significantly higher in steatotic compared with nonsteatotic livers (mean, 33.8% ± 9.4 vs 26.9% ± 8.8; P = .0003). Conclusion: D is significantly decreased in steatosis. The reduction in D * reflects decreased liver parenchymal perfusion in steatosis. Therefore, steatosis can affect diffusion parameters obtained with IVIM. © RSNA, 2012
    Keywords: Gastrointestinal Radiology
    Print ISSN: 0033-8419
    Electronic ISSN: 1527-1315
    Topics: Medicine
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