HH-002 Effectively Suppresses Myeloproliferative Neoplasm Phenotypes in JAK2V617F Transgenic Mice
نویسندگان
چکیده
منابع مشابه
Transgenic expression of JAK2V617F causes myeloproliferative disorders in mice.
The JAK2(V617F) mutation was found in most patients with myeloproliferative disorders (MPDs), including polycythemia vera, essential thrombocythemia, and primary myelofibrosis. We have generated transgenic mice expressing the mutated enzyme in the hematopoietic system driven by a vav gene promoter. The mice are viable and fertile. One line of the transgenic mice, which expressed a lower level o...
متن کاملCardiac hypertrophy associated with myeloproliferative neoplasms in JAK2V617F transgenic mice
BACKGROUND Myeloproliferative neoplasms (MPNs) are blood malignancies manifested in increased production of red blood cells, white blood cells, and/or platelets. A major molecular lesion associated with the diseases is JAK2V617F, an activation mutation form of tyrosine kinase JAK2. Cardiovascular events represent the leading cause of morbidity and mortality associated MPNs, but the underlying m...
متن کاملR723, a selective JAK2 inhibitor, effectively treats JAK2V617F-induced murine myeloproliferative neoplasm.
The activating mutations in JAK2 (including JAK2V617F) that have been described in patients with myeloproliferative neoplasms (MPNs) are linked directly to MPN pathogenesis. We developed R723, an orally bioavailable small molecule that inhibits JAK2 activity in vitro by 50% at a concentration of 2nM, while having minimal effects on JAK3, TYK2, and JAK1 activity. R723 inhibited cytokine-independ...
متن کاملJAK2V617F mRNA metabolism in myeloproliferative neoplasm cell lines
Myeloproliferative neoplasms (MPNs) are a heterogeneous group of leukemias with defective regulation of myeloid stem cell proliferation. They include four distinct diseases: chronic myeloid leukemia, polycythemia vera (PV), essential thrombocythemia (ET) and primary myelofibrosis (PMF). In 2005, four independent studies have concurred to the identification in MPN patients of a specific mutation...
متن کاملEvaluation of JAK2V617F mutation prevalence in myeloproliferative neoplasm by AS-RT-PCR
Abstract Objective JAK2 is a non-receptor tyrosine kinase that plays a major role in myeloid disorders. JAK2V617F mutation is characterized by a G to T transverse at nucleotide 1849 in exon 12 of the JAK2 gene, located on the chromosome 9p, leading to a substitution of valine to phenylalanine at amino acid position 617 in the JAK2 protein. Methods In this study we evaluated RNA from 89 pati...
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ژورنال
عنوان ژورنال: Blood
سال: 2015
ISSN: 0006-4971,1528-0020
DOI: 10.1182/blood.v126.23.4095.4095