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Blood, 15 September 2008, Vol. 112, No. 6, pp. 2190-2198. This Article Full Text Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Citation Map 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 Levine, R. L. Articles by Gilliland, D. G. Search for Related Content PubMed PubMed Citation Articles by Levine, R. L. Articles by Gilliland, D. G. Related Collections Neoplasia Free Research Articles ASH 50th Anniversary Reviews Social Bookmarking                   What's this?  Previous Article  |  Table of Contents  |  Next Article  ASH 50TH ANNIVERSARY REVIEWS Myeloproliferative disorders Ross L. Levine1, and D. Gary Gilliland24 1 Human Oncology and Pathogenesis Program, Leukemia Service, Memorial Sloan-Kettering Cancer Center, New York, NY; 2 Brigham and Women's Hospital, Dana-Farber Cancer Institute, Harvard Medical School, Boston, MA; 3 Howard Hughes Medical Institute, Harvard Stem Cell Institute, Boston, MA; and 4 Broad Institute of Harvard and MIT, Boston, MA In 1951 William Dameshek classified polycythemia vera (PV), essential thombocytosis (ET), and primary myelofibrosis (PMF) as pathogenetically related myeloproliferative disorders (MPD). Subsequent studies demonstrated that PV, ET, and PMF are clonal disorders of multipotent hematopoietic progenitors. In 2005, a somatic activating mutation in the JAK2 nonreceptor tyrosine kinase (JAK2V617F) was identified in most patients with PV and in a significant proportion of patients with ET and PMF. Subsequent studies identified additional mutations in the JAK-STAT pathway in some patients with JAK2V617F– MPD, suggesting that constitutive activation of this signaling pathway is a unifying feature of these disorders. Although the discovery of mutations in the JAK-STAT pathway is important from a pathogenetic and diagnostic perspective, important questions remain regarding the role of this single disease allele in 3 related but clinically distinct disorders, and the role of additional genetic events in MPD disease pathogenesis. In addition, these observations provide a foundation for development of small molecule inhibitors of JAK2 that are currently being tested in clinical trials. This review will discuss our understanding of the pathogenesis of PV, ET, and PMF, the potential role of JAK2-targeted therapy, and the important unanswered questions that need to be addressed to improve clinical outcome. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? This article has been cited by other articles: A. M. Vannucchi, G. Masala, E. Antonioli, M. Chiara Susini, P. Guglielmelli, L. Pieri, L. Maggi, S. Caini, D. Palli, C. Bogani, et al. Increased Risk of Lymphoid Neoplasms in Patients with Philadelphia Chromosome-Negative Myeloproliferative Neoplasms Cancer Epidemiol. Biomarkers Prev., July 1, 2009; 18(7): 2068 - 2073. [Abstract] [Full Text] [PDF] C. G. Mullighan, J. Zhang, R. C. Harvey, J. R. Collins-Underwood, B. A. Schulman, L. A. Phillips, S. K. Tasian, M. L. Loh, X. Su, W. Liu, et al. JAK mutations in high-risk childhood acute lymphoblastic leukemia PNAS, June 9, 2009; 106(23): 9414 - 9418. [Abstract] [Full Text] [PDF] R. L. Levine and M. Carroll A Common Genetic Mechanism in Malignant Bone Marrow Diseases N. Engl. J. Med., May 28, 2009; 360(22): 2355 - 2357. [Full Text] [PDF]

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