title: Clinical correlates of JAK2V617F allele burden in essential thrombocythemia.
abstract: BACKGROUND
  JAK2V617F occurs in approximately 50% of patients with essential thrombocythemia (ET). Qualitative studies of mutation analysis have previously reported an association between JAK2V617F and advanced age, higher hemoglobin level, higher leukocyte count, and lower platelet count. A possible association with thrombotic complication has also been considered.
  
  
  METHODS
  Allele-specific, quantitative polymerase chain reaction (PCR) analysis for JAK2V617F was performed in 176 patients with ET using genomic DNA from archived bone marrow, which was collected within 1 year (n=72 patients), between 1 and 5 years (n=64 patients), or after 5 years (n=40 patients) of diagnosis.
  
  
  RESULTS
  JAK2V617F was detected in 96 patients (55%), in whom mutant allele burden ranged from 1% to 100% (median, 6.3%). Neither mutational frequency (P=.37) nor mutant allele burden (P=.62) was affected by the timing of bone marrow sample collection. The presence of JAK2V617F was found to be significantly associated with higher hemoglobin level (P<.0001), lower platelet count (P=.001), higher leukocyte count (P=.008), increased incidence of venous thrombosis occurring after diagnosis (P=.02), and older age at diagnosis (P=.03). All but age retained significance in multivariable analysis. In mutation-positive patients (n=96 patients), JAK2V617F allele burden clustered between 1% and 22% in 94 cases, in whom it correlated directly and significantly with platelet and leukocyte counts, palpable splenomegaly at diagnosis, and venous thrombosis occurring after diagnosis. The latter 2 associations remained significant with the inclusion of the remaining 2 outlier cases with 100% mutant allele burden; in addition, an association with male gender became evident.
  
  
  CONCLUSIONS
  JAK2V617F allele burden imparts additional phenotypic effects in ET.
authors: Division of Hematology, Department of Medicine, Mayo Clinic, Rochester, Minnesota 55905, USA.
authors: Jaya
authors: J
authors: Kittur
authors: Ryan A
authors: RA
authors: Knudson
authors: Terra L
authors: TL
authors: Lasho
authors: Christy M
authors: CM
authors: Finke
authors: Naseema
authors: N
authors: Gangat
authors: Alexandra P
authors: AP
authors: Wolanskyj
authors: Chin-Yang
authors: CY
authors: Li
authors: Wenting
authors: W
authors: Wu
authors: Rhett P
authors: RP
authors: Ketterling
authors: Animesh
authors: A
authors: Pardanani
authors: Ayalew
authors: A
authors: Tefferi
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000483:Alleles; D001853:Bone Marrow / Q000473:pathology; D004252:DNA Mutational Analysis; D004273:DNA, Neoplasm / Q000032:analysis; D005260:Female; D006801:Humans; D053614:Janus Kinase 2 / Q000235:genetics*; D008297:Male; D008875:Middle Aged; D010641:Phenotype; D010976:Platelet Count; D016133:Polymerase Chain Reaction; D013920:Thrombocythemia, Essential / Q000175:diagnosis / Q000235:genetics*; D020246:Venous Thrombosis / Q000175:diagnosis / Q000235:genetics
chemical_list: D004273:DNA, Neoplasm; C507924:JAK2 protein, human; D053614:Janus Kinase 2