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Blood, 1 June 2005, Vol. 105, No. 11, pp. 4187-4190. Prepublished online as a Blood First Edition Paper on April 7, 2005; DOI 10.1182/blood-2005-03-1287. This Article Full Text (PDF) All Versions of this Article: 2005-03-1287v1 105/11/4187    most recent Alert me when this article is cited Alert me if a correction is posted Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Rights and Permissions Citing Articles Citing Articles via HighWire Citing Articles via CrossRef Citing Articles via Google Scholar Google Scholar Articles by Kaushansky, K. Search for Related Content PubMed PubMed Citation Articles by Kaushansky, K. Related Collections Related Letter in Blood Online Social Bookmarking                   What's this?  Previous Article  |  Next Article  Submitted March 29, 2005 Accepted March 29, 2005 On the Molecular Origins of the Chronic Myeloproliferative Disorders: It All Makes Sense Kenneth Kaushansky* Department of Medicine, Division of Hematology/Oncology, University of California San Diego, San Diego, CA, USA * Corresponding author; email: kkaushansky{at}ucsd.edu. The chronic myeloproliferative diseases, Polycythemia Vera (PV), Essential Thrombocythemia (ET), Idiopathic Myelofibrosis (IMF) and Chronic Myelogenous Leukemia (CML) represent a spectrum of pathogenetically related disorders of varying clinical manifestations. While the origin of CML has been traced to a dysregulated protein kinase, the product of the bcr/abl oncogene, the molecular basis of PV, ET and IMF, which as a group share more similarities with each other than with CML, has been more recalcitrant to solution. However, a major insight into the molecular basis for the enhanced myeloproliferation and clonal dominance that characterizes these disorders is now upon us; four groups of investigators have recently reported that a single, somatic mutation in the protein tyrosine kinase JAK2 appears responsible for many of the features of PV, ET and IMF, an observation that promises to impact the diagnosis and treatment of patients with these disorders, and to spur additional research into the origins of dysregulated cell growth and function. This perspective provides a historical account of the results leading to this landmark finding, and offers observations on the questions that remain unanswered and the opportunities to advance our diagnosis, prognostication and therapy of these challenging disorders of hematopoietic cell regulation. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? 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