title: The Burden of JAK2V617F Mutated Allele in Turkish Patients With Myeloproliferative Neoplasms.
abstract: BACKGROUND
  Studies regarding the impact of JAK2V617F allele burden on phenotypic properties and clinical course in Philadelphia-negative myeloproliferative neoplasms (Ph-negative MPNs) have reported variable results. We aimed to analyze the association of mutated JAK2V617F allele burden with laboratory characteristics and clinical phenotype in Turkish patients (107 essential thrombocythemia (ET) and 77 primary myelofibrosis (PMF)).
  
  
  METHODS
  Peripheral blood samples of 184 patients with Ph-negative MPNs were analyzed for JAK2V617F allele status and burden. JAK2 MutaScreen assay (Ipsogen, Luminy Biotech, Marseille, France) was used to detect the JAK2V617F status and quantitative JAK2V617F allele burdens in genomic DNA using TaqMan allelic discrimination.
  
  
  RESULTS
  Frequency of JAK2V617F-positive patients with high mutation load (allele burden > 50%) was higher in PMF compared to ET (23.4% and 4.7%, respectively; P = 0.001). We found significant association between ET patients with high JAK2V617F allele burden and lower hemoglobin (Hgb) and hematocrit (Hct), higher LDH levels and more prevalent massive splenomegaly (P = 0.001, P = 0.001, P = 0.012 and P = 0.015, respectively). ET patients with high mutation load displayed higher prevalence of bleeding compared to low mutation load and wild-type mutational status (P = 0.003). Rate of DVT was significantly higher in ET patients with mutant allele burden in upper half compared to lower half and wild-type (P = 0.029). We observed significant association between PMF patients with high JAK2V617F allele burden and higher Hgb, Hct levels and leukocyte counts (P = 0.003, P = 0.021 and P = 0.001, respectively).
  
  
  CONCLUSIONS
  Our study demonstrated JAK2V617F allele burden correlates with clinical features in ET and PMF. We conclude quantification of JAK2V617F mutation contributes to the workup of Ph-negative MPNs.
authors.affiliation: Division of Hematology, Department of Internal Medicine, Istanbul University Istanbul Medical Faculty, Fatih, Istanbul, Turkey.
authors.forename: Ipek
authors.initials: I
authors.lastname: Yonal-Hindilerden
authors.affiliation: Division of Hematology, Department of Internal Medicine, Istanbul University Istanbul Medical Faculty, Fatih, Istanbul, Turkey.
authors.forename: Aynur
authors.initials: A
authors.lastname: Daglar-Aday
authors.affiliation: Division of Hematology, Department of Internal Medicine, Istanbul University Istanbul Medical Faculty, Fatih, Istanbul, Turkey.
authors.forename: Basak
authors.initials: B
authors.lastname: Akadam-Teker
authors.affiliation: Division of Hematology, Department of Internal Medicine, Istanbul University Istanbul Medical Faculty, Fatih, Istanbul, Turkey.
authors.forename: Ceylan
authors.initials: C
authors.lastname: Yilmaz
authors.affiliation: Division of Hematology, Department of Internal Medicine, Istanbul University Istanbul Medical Faculty, Fatih, Istanbul, Turkey.
authors.forename: Meliha
authors.initials: M
authors.lastname: Nalcaci
authors.affiliation: Division of Hematology, Department of Internal Medicine, Istanbul University Istanbul Medical Faculty, Fatih, Istanbul, Turkey.
authors.forename: Akif Selim
authors.initials: AS
authors.lastname: Yavuz
authors.affiliation: Division of Hematology, Department of Internal Medicine, Istanbul University Istanbul Medical Faculty, Fatih, Istanbul, Turkey.
authors.forename: Deniz
authors.initials: D
authors.lastname: Sargin
keywords: Essential thrombocythemia; JAK2V617F allele burden; JAK2V617F allele status; Philadelphia-negative myeloproliferative neoplasms; Primary myelofibrosis