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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 cytokineindependent CFU-E growth and constitutive activation of STAT5 in primary hematopoietic cells expressing JAK2V617F. In an anemia mouse model induced by phenylhydrazine, R723 inhibited erythropoiesis. In a leukemia mouse model using Ba/F3 cells expressing JAK2V617F, R723 treatment prolonged survival and decreased tumor burden. In V617F-transgenic mice that closely mimic human primary myelofibrosis, R723 treatment improved survival, hepatosplenomegaly, leukocytosis, and thrombocytosis. R723 preferentially targeted the JAK2-dependent pathway rather than the JAK1-and JAK3-dependent pathways in vivo, and its effects on T and B lymphocytes were mild compared with its effects on myeloid cells. Our preclinical data indicate that R723 has a favorable safety profile and the potential to become an efficacious treatment for patients with JAK2V617F-positive MPNs. (Blood. 2011;117(25):6866-6875)

ELIZABETH TONKIN, Narrating our pasts: The social construction of distinctions and categories in the study of oral history, and for taking a Narrating our Pasts: The Social Construction of Oral History Nursing Research Using Historical Methods: Qualitative Designs and .-Google Books Result Narrating Our Past: The Social Construction of Oral History. ELIZABETH TONKIN, Narrating our pasts: The social construction of oral history. (Cambridge studies in oral and literate culture, 22.) Cambridge & New York: Narrating our pasts: the social construction of oral history University. In this book, Elizabeth Tonkin. .. uses an interdisciplinary approach to investigate the construction and interpretation of oral histories.