title: The Clinical Significance of IDH Mutations in Essential Thrombocythemia and Primary Myelofibrosis.
abstract: BACKGROUND
  Limited data exist regarding impact of IDH mutations in Philadelphia-negative myeloproliferative neoplasms (Ph-negative MPNs). Prognostic significance of IDH mutations was asessed in 184 Ph-negative MPN patients - 107 essential thrombocythemia (ET) and 77 primary myelofibrosis (PMF).
  
  
  METHODS
  High-resolution melting (HRM) analysis was used to detect IDH1 and IDH2 mutations.
  
  
  RESULTS
  PMF and ET patients showed no significant difference for prevalence of IDH mutations. Mutant IDH (IDH1 or IDH2) was documented in five of PMF (6.5%) and two of ET patients (1.9%). IDH mutations in ET patients included one IDH1 R132C and one IDH2 R140Q. Of the five IDH-mutated PMF patients, four (80%) displayed IDH1 (three IDH1 R132C and one IDH1 R132S) and one (20%) carried IDH2 (IDH2 R140Q) mutation. Sixty percent (three in five) of IDH-mutated PMF patients carried JAK2V617F with following allele burdens: 31-50%, 5-12.5% and 31-50%, respectively. Three of 77 PMF patients (3.9%) simultaneously harbored IDH and JAK2V617F mutations. IDH mutations in PMF showed a trend towards higher rate in females (100% and 52.8%, respectively). Bleeding complications were significantly higher in IDH-mutated PMF patients compared to IDH wild-type counterparts. Trend towards a lower prevalance of acetylsalicylic acid (ASA) use was present in IDH mutant PMF patients compared to wild-type counterparts (20% and 63.9%, respectively). Death rate was higher in IDH-mutated PMF patients compared to IDH wild-type PMF patients (60% and 15.3%). In univariate analysis, a significantly shorter leukemia-free survival (LFS) was observed in IDH-mutated PMF patients.
  
  
  CONCLUSIONS
  We conclude that IDH mutations indicate a risk for leukemic transformation in PMF.
authors.affiliation: Division of Hematology, Department of Internal Medicine, Istanbul University Istanbul Medical Faculty, 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, Istanbul, Turkey.
authors.forename: Aynur
authors.initials: A
authors.lastname: Daglar-Aday
authors.affiliation: Hematology Clinic, Istanbul Bakirkoy Sadi Konuk Training and Research Hospital, Istanbul, Turkey.
authors.forename: Fehmi
authors.initials: F
authors.lastname: Hindilerden
authors.affiliation: Division of Hematology, Department of Internal Medicine, Istanbul University Istanbul Medical Faculty, 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, 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, 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, Istanbul, Turkey.
authors.forename: Akif Selim
authors.initials: AS
authors.lastname: Yavuz
authors.affiliation: Division of Hematology, Department of Internal Medicine, Medipol University, Istanbul, Turkey.
authors.forename: Deniz
authors.initials: D
authors.lastname: Sargin
keywords: IDH1; IDH2; Philadelphia-negative myeloproliferative neoplasms