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Blood, 1 July 2008, Vol. 112, No. 1, pp. 141-149. Prepublished online as a Blood First Edition Paper on May 1, 2008; DOI 10.1182/blood-2008-01-131664. This Article Full Text Full Text (PDF) Supplemental Figure All Versions of this Article: blood-2008-01-131664v1 112/1/141    most recent 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 Beer, P. A. Articles by Green, A. R. Search for Related Content PubMed PubMed Citation Articles by Beer, P. A. Articles by Green, A. R. Related Collections Neoplasia Free Research Articles Clinical Trials and Observations Social Bookmarking                   What's this?  Previous Article  |  Table of Contents  |  Next Article  NEOPLASIA MPL mutations in myeloproliferative disorders: analysis of the PT-1 cohort Philip A. Beer1,2, Peter J. Campbell2,3, Linda M. Scott1, Anthony J. Bench2, Wendy N. Erber2, David Bareford4, Bridget S. Wilkins5, John T. Reilly6, Hans C. Hasselbalch7, Richard Bowman8, Keith Wheatley9, Georgina Buck10, Claire N. Harrison11, and Anthony R. Green1,2 1 Department of Haematology, University of Cambridge, Cambridge, United Kingdom; 2 Department of Haematology, Addenbrooke's Hospital, Cambridge, United Kingdom; 3 Wellcome Trust Sanger Institute, Duxford, United Kingdom; 4 Department of Haematology, Russell's Hall Hospital, Dudley, United Kingdom; 5 Department of Pathology, Royal Victoria Infirmary, Newcastle, United Kingdom; 6 Department of Haematology, Royal Hallamshire Hospital, Sheffield, United Kingdom; 7 Department of Haematology and Pathology, Odense University Hospital, Odense, Denmark; 8 Medical Research Council (MRC) Dunn Nutrition Unit, University of Cambridge, Cambridge, United Kingdom; 9 Birmingham Clinical Trials Unit, Birmingham, United Kingdom; 10 Clinical Trials Service Unit, Oxford, United Kingdom; and 11 Department of Haematology, St Thomas's Hospital, London, United Kingdom Activating mutations of MPL exon 10 have been described in a minority of patients with idiopathic myelofibrosis (IMF) or essential thrombocythemia (ET), but their prevalence and clinical significance are unclear. Here we demonstrate that MPL mutations outside exon 10 are uncommon in platelet cDNA and identify 4 different exon 10 mutations in granulocyte DNA from a retrospective cohort of 200 patients with ET or IMF. Allele-specific polymerase chain reaction was then used to genotype 776 samples from patients with ET entered into the PT-1 studies. MPL mutations were identified in 8.5% of JAK2 V617F– patients and a single V617F+ patient. Patients carrying the W515K allele had a significantly higher allele burden than did those with the W515L allele, suggesting a functional difference between the 2 variants. Compared with V617F+ ET patients, those with MPL mutations displayed lower hemoglobin and higher platelet levels at diagnosis, higher serum erythropoietin levels, endogenous megakaryocytic but not erythroid colony growth, and reduced bone marrow erythroid and overall cellularity. Compared with V617F– patients, those with MPL mutations were older with reduced bone marrow cellularity but could not be identified as a discrete clinicopathologic subgroup. MPL mutations lacked prognostic significance with respect to thrombosis, major hemorrhage, myelofibrotic transformation or survival. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? This article has been cited by other articles: P. J. Campbell, D. Bareford, W. N. Erber, B. S. Wilkins, P. Wright, G. Buck, K. Wheatley, C. N. Harrison, and A. R. Green Reticulin Accumulation in Essential Thrombocythemia: Prognostic Significance and Relationship to Therapy J. Clin. Oncol., June 20, 2009; 27(18): 2991 - 2999. [Abstract] [Full Text] [PDF] G. Barosi, G. Birgegard, G. Finazzi, M. Griesshammer, C. Harrison, H. C. Hasselbalch, J.-J. Kiladjian, E. Lengfelder, M. F. McMullin, F. Passamonti, et al. Response criteria for essential thrombocythemia and polycythemia vera: result of a European LeukemiaNet consensus conference Blood, May 14, 2009; 113(20): 4829 - 4833. [Abstract] [Full Text] [PDF] C. Marty, R. Chaligne, C. Lacout, S. N. Constantinescu, W. Vainchenker, and J.-L. Villeval Ligand-independent Thrombopoietin Mutant Receptor Requires Cell Surface Localization for Endogenous Activity J. Biol. Chem., May 1, 2009; 284(18): 11781 - 11791. [Abstract] [Full Text] [PDF] A. M. Vannucchi, P. Guglielmelli, and A. Tefferi Advances in Understanding and Management of Myeloproliferative Neoplasms CA Cancer J Clin, May 1, 2009; 59(3): 171 - 191. [Abstract] [Full Text] [PDF] S. Schnittger, U. Bacher, C. Haferlach, T. Geer, P. Muller, J. Mittermuller, P. Petrides, R. Schlag, R. Sandner, J. Selbach, et al. Detection of JAK2 exon 12 mutations in 15 patients with JAK2V617F negative polycythemia vera Haematologica, March 1, 2009; 94(3): 414 - 418. [Abstract] [Full Text] [PDF] R. Tiedt, J. Coers, S. Ziegler, A. Wiestner, H. Hao-Shen, C. Bornmann, J. Schenkel, S. Karakhanova, F. J. de Sauvage, C. W. Jackson, et al. Pronounced thrombocytosis in transgenic mice expressing reduced levels of Mpl in platelets and terminally differentiated megakaryocytes Blood, February 19, 2009; 113(8): 1768 - 1777. [Abstract] [Full Text] [PDF] S. Schnittger, U. Bacher, C. Haferlach, D. Beelen, P. Bojko, D. Burkle, R. Dengler, A. Distelrath, M. Eckart, R. Eckert, et al. Characterization of 35 new cases with four different MPLW515 mutations and essential thrombocytosis or primary myelofibrosis Haematologica, January 1, 2009; 94(1): 141 - 144. [Full Text] [PDF] P. Guglielmelli, G. Barosi, L. Pieri, E. Antonioli, A. Bosi, and A. M. Vannucchi JAK2V617F mutational status and allele burden have little influence on clinical phenotype and prognosis in patients with post-polycythemia vera and post-essential thrombocythemia myelofibrosis Haematologica, January 1, 2009; 94(1): 144 - 146. 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