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Blood, 1 March 2008, Vol. 111, No. 5, pp. 2785-2789. Prepublished online as a Blood First Edition Paper on November 15, 2007; DOI 10.1182/blood-2007-06-095703. This Article Full Text (PDF) Supplemental Methods and Tables All Versions of this Article: blood-2007-06-095703v1 111/5/2785    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 Pardanani, A. Articles by Tefferi, A. Search for Related Content PubMed PubMed Citation Articles by Pardanani, A. Articles by Tefferi, A. Related Collections Related Article in Blood Online Social Bookmarking                   What's this?  Previous Article  |  Next Article  Submitted June 13, 2007 Accepted November 9, 2007 Host genetic variation contributes to phenotypic diversity in myeloproliferative disorders Animesh Pardanani*, Brooke L Fridley, Terra L Lasho, D Gary Gilliland, and Ayalew Tefferi Division of Hematology, Mayo Clinic, Rochester, MN, United States Division of Biostatistics, Mayo Clinic, Rochester, MN, United States Brigham and Women's Hospital and Dana-Farber Cancer Institute, & Howard Hughes Medical Institute, Harvard Medical School, Boston, MA, United States * Corresponding author; email: pardanani.animesh{at}mayo.edu. JAK2V617F is an acquired mutation associated with polycythemia vera (PV), essential thrombocythemia (ET), and primary myelofibrosis (PMF). We tested the hypothesis that the paradox of a single disease allele associated with three distinctive clinical phenotypes could be explained in part by host modifying influences. We screened for genetic variation within four candidate genes involved in JAK-STAT signaling, including receptors for erythropoietin (EPOR), thrombopoietin (MPL), and granulocyte colony stimulating factor (GCSFR), and JAK2. We genotyped 32 linkage disequilibrium tag single nucleotide polymorphism (SNP) loci in 179 Caucasian patients-84 had PV, 58 PMF, and 37 ET. Genotype-phenotype analysis showed three JAK2 SNPs (rs7046736, rs10815148, rs12342421) to be significantly, but reciprocally associated with PV (p=0.000004, 0.000002, and 0.00006; odds ratio = 0.16, 2.72, and 2.46, respectively) and ET (p = 0.0007, 0.00019, and 0.00125; odds ratio = 3.05, 0.29, and 0.30, respectively), but not PMF. Three additional JAK2 SNPs (rs10758669, rs3808850, rs10974947) and a single EPOR SNP (rs318699) were also significantly associated with PV, but not ET or PMF. Finally, intragene haplotypes in JAK2 were significantly associated with PV only. Thus, host genetic variation may contribute to phenotypic diversity among myeloproliferative disorders, including in the presence of a shared disease allele. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? Related Article in Blood Online: JAK2: how many faces in MPDs? Alessandro M. Vannucchi Blood 2008 111: 2499. [Full Text] [PDF] This article has been cited by other articles: C. Saint-Martin, G. Leroy, F. Delhommeau, G. Panelatti, S. Dupont, C. James, I. Plo, D. Bordessoule, C. Chomienne, A. Delannoy, et al. Analysis of the Ten-Eleven Translocation 2 (TET2) gene in familial myeloproliferative neoplasms Blood, August 20, 2009; 114(8): 1628 - 1632. [Abstract] [Full Text] [PDF] 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] 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] F. Passamonti and E. Rumi Clinical relevance of JAK2 (V617F) mutant allele burden Haematologica, January 1, 2009; 94(1): 7 - 10. [Full Text] [PDF] R. L. Levine and D. G. Gilliland Myeloproliferative disorders Blood, September 15, 2008; 112(6): 2190 - 2198. [Abstract] [Full Text] [PDF] O. Landgren, L. R. Goldin, S. Y. Kristinsson, E. A. Helgadottir, J. Samuelsson, and M. Bjorkholm Increased risks of polycythemia vera, essential thrombocythemia, and myelofibrosis among 24 577 first-degree relatives of 11 039 patients with myeloproliferative neoplasms in Sweden Blood, September 15, 2008; 112(6): 2199 - 2204. [Abstract] [Full Text] [PDF] K. Van Pelt, F. Nollet, D. Selleslag, L. Knoops, S. N. Constantinescu, A. Criel, and J. Billiet The JAK2V617F mutation can occur in a hematopoietic stem cell that exhibits no proliferative advantage: a case of human allogeneic transplantation Blood, August 1, 2008; 112(3): 921 - 922. [Full Text] [PDF] A. M. Vannucchi and P. Guglielmelli Molecular pathophysiology of Philadelphia-negative myeloproliferative disorders: beyond JAK2 and MPL mutations Haematologica, July 1, 2008; 93(7): 972 - 976. [Full Text] [PDF] R. L. Levine JAK2V617F: you can't have too much Blood, April 15, 2008; 111(8): 3913 - 3913. [Full Text] [PDF] C. James The JAK2V617F Mutation in Polycythemia Vera and Other Myeloproliferative Disorders: One Mutation for Three Diseases? Hematology, January 1, 2008; 2008(1): 69 - 75. [Abstract] [Full Text] [PDF] R. L. Levine and M. Heaney New Advances in the Pathogenesis and Therapy of Essential Thrombocythemia Hematology, January 1, 2008; 2008(1): 76 - 82. [Abstract] [Full Text] [PDF]

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