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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 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 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 Pardanani, A. Articles by Tefferi, A. Search for Related Content PubMed PubMed Citation Articles by Pardanani, A. Articles by Tefferi, A. Related Collections Neoplasia Related Article in Blood Online Social Bookmarking                   What's this?  Previous Article  |  Table of Contents  |  Next Article  NEOPLASIA Host genetic variation contributes to phenotypic diversity in myeloproliferative disorders Animesh Pardanani1, Brooke L. Fridley2, Terra L. Lasho1, D. Gary Gilliland3,4, and Ayalew Tefferi1 Divisions of1 Hematology and 2 Biostatistics, Mayo Clinic, Rochester, MN; 3 Brigham and Women's Hospital and Dana-Farber Cancer Institute, Harvard Medical School, Boston, MA; and 4 Howard Hughes Medical Institute, Harvard Medical School, Boston, MA 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 3 distinctive clinical phenotypes could be explained in part by host-modifying influences. We screened for genetic variation within 4 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 white patients: 84 had PV, 58 had PMF, and 37 had ET. Genotype-phenotype analysis showed 3 JAK2 SNPs (rs7046736, rs10815148, and rs12342421) to be significantly but reciprocally associated with PV (P < .001 for all; odds ratio = 0.16, 2.72, and 2.46, respectively) and ET (P < .001 for all; odds ratio = 3.05, 0.29, and 0.30, respectively) but not with PMF. Three additional JAK2 SNPs (rs10758669, rs3808850, and rs10974947) and a single EPOR SNP (rs318699) were also significantly associated with PV but not with 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: 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]

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