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Score J Hidalgo-Curtis C Jones AV Winkelmann N Skinner A Ward D Zoi K Ernst T Stegelmann F Döhner K Chase A Cross NC 《Blood》2012,119(5):1208-1213
The polycomb repressive complex 2 (PRC2) is a highly conserved histone H3 lysine 27 methyltransferase that regulates the expression of developmental genes. Inactivating mutations of the catalytic component of PRC2, EZH2, are seen in myeloid disorders. We reasoned that the other 2 core PRC2 components, SUZ12 and EED, may also be mutational targets in these diseases, as well as associated factors such as JARID2. SUZ12 mutations were identified in 1 of 2 patients with myelodysplastic syndrome/myeloproliferative neoplasms with 17q acquired uniparental disomy and in 2 of 2 myelofibrosis cases with focal 17q11 deletions. All 3 were missense mutations affecting the highly conserved VEFS domain. Analysis of a further 146 myelodysplastic syndrome/myeloproliferative neoplasm patients revealed an additional VEFS domain mutant, yielding a total mutation frequency of 1.4% (2 of 148). We did not find mutations of JARID2 or EED in association with acquired uniparental disomy for chromosome 6p or 11q, respectively; however, screening unselected cases identified missense mutations in EED (1 of 148; 1%) and JARID2 (3 of 148; 2%). All 3 SUZ12 mutations tested and the EED mutation reduced PRC2 histone methyltransferase activity in vitro, demonstrating that PRC2 function may be compromised in myeloid disorders by mutation of distinct genes. 相似文献
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Amit Batla Maria Stamelou Katerina Mensikova Michaela Kaiserova Lucie Tuckova Petr Kanovsky Niall Quinn Kailash P. Bhatia 《Parkinsonism & related disorders》2013,19(10):901-905
BackgroundMultiple system atrophy (MSA) presents with fairly symmetrical, levodopa unresponsive parkinsonism and additional features like autonomic dysfunction, cerebellar and corticospinal tract involvement. Marked asymmetry in atypical parkinsonism suggests alternative diagnosis like Corticobasal syndrome (CBS).MethodsWe describe five unusual cases, who presented initially with markedly asymmetric parkinsonism, rigid dystonic abnormal limb posturing and subsequently developed clinical and/or radiological features consistent with probable MSA-P.ResultsUsing the internationally accepted diagnostic criteria, the patients fulfilled the diagnostic criteria for probable MSA-P after 5 years from disease onset. Case 4 and 5 had characteristic MRI features and Case 2 was pathologically confirmed.ConclusionsWe use these cases to highlight that MSA-P MSA-P can present rarely with very marked asymmetry, dystonic limb and myoclonic jerks leading to a diagnosis of CBS at onset. 相似文献
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Lejhancova-Tousovska K Zapletal O Vytiskova S Strbackova P Sterba J 《Blood coagulation & fibrinolysis》2012,23(2):144-154
Treatment with L-asparaginase is associated with coagulation disturbances with deep venous thrombosis being the most common clinical consequence. Use of the calibrated automated thrombogram allows precise estimation of thrombin generated in vitro. We show the first data on thrombin generation, measured by calibrated automated thrombography (CAT), in children with acute lymphoblastic leukemia treated with L-asparaginase. Thrombin generation was measured by means of CAT in 23 children treated for acute lymphoblastic leukemia. Samples were obtained at predefined time points during the induction and reinduction phase of acute lymphoblastic leukemia-intercontinental Berlin-Frankfurt-Münster (BFM) 2000 or Associazione Italiana Ematologica Oncologia Pedaitrica Interim BFM 2000 protocols. Antihrombin and fibrinogen were measured on the same sample. Twenty-eight sets of thrombin generation measurements were collected from 23 patients. We observed no significant effect of antithrombin deficiency and/or hypofibrinogenemia on thrombin generation. Endogenous thrombin generation and peak thrombin were significantly higher during induction than in the reinduction phase (P?0.001). Four patients with severe infection experienced an increase in thrombin generation, reaching maximum in a median of 7.5 days after the onset of infection. Two of those patients developed deep venous thrombosis at the time of peaked endogenous thrombin generation. Thrombin generation in children with acute lymphoblastic leukemia treated according to BFM protocols is significantly higher during the induction phase compared with reinduction and is not substantially affected by hypofibrinogenemia and/or antithrombin deficiency. Severe infection during the induction phase enhances thrombin generation with subsequent risk of thrombosis. 相似文献
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