title: Clonal analyses reveal associations of JAK2V617F homozygosity with hematologic features, age and gender in polycythemia vera and essential thrombocythemia.
abstract: Subclones homozygous for JAK2V617F are more common and larger in patients with polycythemia vera compared to essential thrombocythemia, but their role in determining phenotype remains unclear. We genotyped 4564 erythroid colonies from 59 patients with polycythemia vera or essential thrombocythemia to investigate whether the proportion of JAK2V617F -homozygous precursors, compared to heterozygous precursors, is associated with clinical or demographic features. In polycythemia vera, a higher proportion of homozygous-mutant precursors was associated with more extreme blood counts at diagnosis, consistent with a causal role for homozygosity in polycythemia vera pathogenesis. Larger numbers of homozygous-mutant colonies were associated with older age, and with male gender in polycythemia vera but female gender in essential thrombocythemia. These results suggest that age promotes development or expansion of homozygous-mutant clones and that gender modulates the phenotypic consequences of JAK2V617F homozygosity, thus providing a potential explanation for the long-standing observations of a preponderance of men with polycythemia vera but of women with essential thrombocythemia.
authors: Cambridge Institute for Medical Research and Department of Haematology, University of Cambridge, Cambridge, UK.
authors: Anna L
authors: AL
authors: Godfrey
authors: Edwin
authors: E
authors: Chen
authors: Francesca
authors: F
authors: Pagano
authors: Yvonne
authors: Y
authors: Silber
authors: Peter J
authors: PJ
authors: Campbell
authors: Anthony R
authors: AR
authors: Green
mesh_terms: D000367:Age Factors; D004909:Erythrocyte Indices; D005260:Female; D006720:Homozygote; D006801:Humans; D053614:Janus Kinase 2 / Q000235:genetics*; D007958:Leukocyte Count; D008297:Male; D008957:Models, Genetic; D009154:Mutation; D010976:Platelet Count; D011087:Polycythemia Vera / Q000097:blood* / Q000235:genetics*; D012737:Sex Factors; D013920:Thrombocythemia, Essential / Q000097:blood* / Q000235:genetics*
chemical_list: D053614:Janus Kinase 2
references: N Engl J Med. 2006 Dec 7;355(23):2452-66
references: 17151367
references: Ann Intern Med. 1995 Nov 1;123(9):656-64
references: 7574220
references: Eur J Haematol. 2000 Aug;65(2):132-9
references: 10966175
references: Nature. 2007 Jun 7;447(7145):725-9
references: 17554309
references: Haematologica. 2008 Aug;93(8):1260-1
references: 18519514
references: Blood. 2007 Aug 1;110(3):840-6
references: 17379742
references: Curr Biol. 2006 Oct 24;16(20):2009-15
references: 17055979
references: Blood. 2007 Aug 1;110(3):1013-21
references: 17389763
references: Leukemia. 2008 Jul;22(7):1299-307
references: 18496562
references: Blood. 2010 Sep 2;116(9):1528-38
references: 20489053
references: Blood. 2012 Sep 27;120(13):2704-7
references: 22898600
references: Blood. 2010 Apr 29;115(17):3589-97
references: 20197548
references: Cancer Cell. 2010 Nov 16;18(5):524-35
references: 21074499
references: Blood. 2006 Sep 1;108(5):1652-60
references: 16670266
references: Blood. 2008 Apr 15;111(8):3931-40
references: 18160670
references: Br J Haematol. 2011 Feb;152(4):413-9
references: 21219298
references: Science. 2003 Sep 26;301(5641):1908-11
references: 14512629
references: Br J Haematol. 2010 May;149(3):352-75
references: 20331456
references: Blood. 2006 Oct 1;108(7):2435-7
references: 16772604
references: Br J Haematol. 2007 Sep;138(6):821-2
references: 17672880
references: Blood. 2010 Aug 5;116(5):783-7
references: 20472827
references: Haematologica. 2010 Jul;95(7):1090-7
references: 20133898
references: Cancer Cell. 2010 Jun 15;17(6):584-96
references: 20541703
references: Leukemia. 2010 Sep;24(9):1574-9
references: 20631743