title: The clinical phenotype of wild-type, heterozygous, and homozygous JAK2V617F in polycythemia vera.
abstract: BACKGROUND
  Several studies have recently reported on the occurrence of a JAK2(V617F) mutation in myeloid cells from the majority of patients with polycythemia vera (PV). The clinical relevance of this novel observation currently is under study.
  
  
  METHODS
  In a single institutional study, mutation screening for JAK2(V617F) was performed in DNA derived from archived blood granulocytes from 63 consecutive patients with PV in whom current diagnostic criteria were strictly applied and the diagnosis confirmed by bone marrow histology.
  
  
  RESULTS
  The JAK2(V617F) mutant allele was detected in 58 of the 63 patients (92%) with 21% homozygosity. The clinical phenotype of the five patients with the wild-type allele was otherwise typical for the disease. A statistical comparison between JAK2(V617F) heterozygotes (n=45 patients) and homozygotes (n=13 patients) did not reveal any significant associations with regard to age, gender, leukocyte or platelet count at the time of diagnosis, duration of disease, or the incidences of thrombosis or bleeding. However, compared with their heterozygote counterparts, JAK2(V617F) homozygote patients displayed a significantly higher hemoglobin level at the time of diagnosis (P=0.001), an increased incidence of pruritus (69% vs. 38%; P=0.04), a higher rate of fibrotic transformation (23% vs. 2%; P=0.009), and higher PRV-1 transcript levels in their blood granulocytes (P=0.07).
  
  
  CONCLUSIONS
  The results of the current clinical study support previous laboratory observations that link JAK2(V617F) with the PV phenotype by demonstrating a mutant allele dose effect on erythrocytosis and clinical and laboratory features characteristic of PV.
authors.affiliation: Division of Hematology and Laboratory Medicine, Mayo Clinic, Rochester, Minnesota 55905, and Department of Oncology, Dana-Farber Cancer Institute, Harvard Medical School, Boston, MA, USA. tefferi.ayalew@mayo.edu
authors.forename: Ayalew
authors.initials: A
authors.lastname: Tefferi
authors.forename: Terra L
authors.initials: TL
authors.lastname: Lasho
authors.forename: Susan M
authors.initials: SM
authors.lastname: Schwager
authors.forename: Jacob S
authors.initials: JS
authors.lastname: Strand
authors.forename: Michelle
authors.initials: M
authors.lastname: Elliott
authors.forename: Ruben
authors.initials: R
authors.lastname: Mesa
authors.forename: Chin-Yang
authors.initials: CY
authors.lastname: Li
authors.forename: Martha
authors.initials: M
authors.lastname: Wadleigh
authors.forename: Stephanie J
authors.initials: SJ
authors.lastname: Lee
authors.forename: D Gary
authors.initials: DG
authors.lastname: Gilliland
mesh_terms: D000293:Adolescent; D000328:Adult; D000367:Age Factors; D000368:Aged; D000369:Aged, 80 and over; D004252:DNA Mutational Analysis; D004273:DNA, Neoplasm / Q000032:analysis; D018450:Disease Progression; D005260:Female; D058851:GPI-Linked Proteins; D006098:Granulocytes; D006454:Hemoglobins / Q000032:analysis; D006801:Humans; D007519:Isoantigens / Q000097:blood; D053614:Janus Kinase 2; D008297:Male; D008562:Membrane Glycoproteins / Q000097:blood; D008875:Middle Aged; D010641:Phenotype; D011087:Polycythemia Vera / Q000235:genetics* / Q000473:pathology; D011505:Protein-Tyrosine Kinases / Q000235:genetics*; D011518:Proto-Oncogene Proteins / Q000235:genetics*; D011537:Pruritus / Q000209:etiology; D011956:Receptors, Cell Surface / Q000097:blood
chemical_list: C407242:CD177 protein, human; D004273:DNA, Neoplasm; D058851:GPI-Linked Proteins; D006454:Hemoglobins; D007519:Isoantigens; D008562:Membrane Glycoproteins; D011518:Proto-Oncogene Proteins; D011956:Receptors, Cell Surface; D011505:Protein-Tyrosine Kinases; C507924:JAK2 protein, human; D053614:Janus Kinase 2