MYELOID NEOPLASIA CYT387, a novel JAK2 inhibitor, induces hematologic responses and normalizes inflammatory cytokines in murine myeloproliferative neoplasms
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چکیده
1Knight Cancer Institute, Oregon Health & Science University, Portland; 2Department of Radiation Medicine, School of Medicine, School of Nursing, Oregon Health & Science University, Portland; 3Department of Internal Medicine I, Division of Hematology and Hemostaseology, Medical University of Vienna, Vienna, Austria; 4Department of Pathology, Oregon Health & Science University, Portland; 5Howard Hughes Medical Institute; and 6YM Biosciences Australia Pty Ltd (formerly Cytopia Research Pty Ltd), Melbourne, Australia
منابع مشابه
CYT387, a novel JAK2 inhibitor, induces hematologic responses and normalizes inflammatory cytokines in murine myeloproliferative neoplasms.
Activating alleles of Janus kinase 2 (JAK2) such as JAK2(V617F) are central to the pathogenesis of myeloproliferative neoplasms (MPN), suggesting that small molecule inhibitors targeting JAK2 may be therapeutically useful. We have identified an aminopyrimidine derivative (CYT387), which inhibits JAK1, JAK2, and tyrosine kinase 2 (TYK2) at low nanomolar concentrations, with few additional target...
متن کاملCYT387, A NOVEL JAK2 INHIBITOR, INDUCES HEMATOLOGIC RESPONSES AND NORMALIZES INFLAMMATORY CYTOKINES IN MURINE MYELOPROLIFERATIVE NEOPLASMS Running Title: Novel JAK2 Inhibitor for MPN
Oregon Health & Sciences University Knight Cancer Institute, Portland, OR 97239, USA Oregon Health & Sciences University School of Nursing, School of Medicine, Department of Radiation Medicine, Portland, OR 97239, USA 3 Department of Internal Medicine I, Division of Hematology and Hemostaseology, Medical University of Vienna, Austria Oregon Health & Science University Department of Pathology, P...
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MPNs including a heterogeneous group of clonal or oligoclonal hamtopathies characterized by proliferation and accumulation of mature myeloid cells. JAK2 tyrosine kinase mutation is the most common molecular lesion identified in 90% of cases. JAK2 is involved in EPO signaling pathway, and mutations in it lead to EPO-independent spontaneous phosphorylation. Most tyrosine kinase inhibitors (TKI) a...
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PURPOSE Deregulation of the Janus kinase-signal transducers and activators of transcription (JAK-STAT) pathway is a hallmark for the Philadelphia chromosome-negative myeloproliferative diseases polycythemia vera, essential thrombocythemia, and primary myelofibrosis. We tested the efficacy of a selective JAK1/2 inhibitor in cellular and in vivo models of JAK2-driven malignancy. EXPERIMENTAL DE...
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Eosinophilia in the absence of allergies, asthma, drug reactions, parasitic infections and connective tissue diseases can be eosinophilic clonal disorders, lymphoma or myeloproliferative disorders. Hypereosinophilia with the persistence of eosinophils ≥1500 /mm³ in blood or more than 20% of eosinophils in the bone marrow may be observed in many reactive or clonal disorders, the result of which ...
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تاریخ انتشار 2010