Acute myeloid leukaemia(AML)patients harbouring certain chromosome abnormalities have particularly adverse *** these patients,targeted therapies have not yet made a significant clinical *** understand the molecular la...
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Acute myeloid leukaemia(AML)patients harbouring certain chromosome abnormalities have particularly adverse *** these patients,targeted therapies have not yet made a significant clinical *** understand the molecular landscape of poor prognosis AML we profiled 74 patients from two different centres(in UK and Finland)at the proteomic,phosphoproteomic and drug response phenotypic *** data were complemented with transcriptomics analysis for 39 *** integration highlighted a phosphoproteomics signature that define two biologically distinct groups of KMT2A rearranged leukaemia,which we term MLLGA and *** presented increased DOT1L phosphorylation,HOXA gene expression,CDK1 activity and phosphorylation of proteins involved in RNA metabolism,replication and DNA damage when compared to MLLGB and no KMT2A rearranged *** was particularly sensitive to 15 compounds including genotoxic drugs and inhibitors of mitotic kinases and inosine-5-monosphosphate dehydrogenase(IMPDH)relative to other ***-risk KMT2A-MLLT3 cases were mainly represented in a third group closer to MLLGA than to *** expression of IMPDH2 and multiple nucleolar proteins was higher in MLLGA and correlated with the response to IMPDH inhibition in KMT2A rearranged leukaemia,suggesting a role of the nucleolar activity in sensitivity to *** summary,our multilayer molecular profiling of AML with poor prognosis and KMT2A-MLLT3 karyotypes identified a phosphoproteomics signature that defines two biologically and phenotypically distinct groups of KMT2A rearranged *** data provide a rationale for the potential development of specific therapies for AML patients characterised by the MLLGA phosphoproteomics signature identified in this study.
Background and Purpose-We sought to examine ischemic stroke subtypes and prevalence of thrombophilia in Brazilian stroke patients. Method-A total of 130 consecutive young and 200 elderly stroke patients were studied. ...
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Background and Purpose-We sought to examine ischemic stroke subtypes and prevalence of thrombophilia in Brazilian stroke patients. Method-A total of 130 consecutive young and 200 elderly stroke patients were studied. Results-Prevalence of thrombophilia was, respectively: protein S deficiency (11.5%versus 5.5%), protein C deficiency (0.76%versus 1%), resistance to activated protein C (2.3%versus 3.5%), mutation in V Leiden factor (1.5%versus 2%), antithrombin III deficiency (0%versus 0%), lupus anticoagulant (0%versus 0.5%), anticardiolipin antibodies (3%versus 10%; P=0.01), hyperhomocysteinemia (31.5%versus 53.5%; P=0.0001), mutation of the MTHFR gene in homocigosis (10%versus 5%), and heterocigosis (27.6%versus 41.9%; P=0.01). Conclusion -Prothrombotic conditions were more frequent in stroke of undetermined cause.
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