title: The prognostic impact of germline 46/1 haplotype of Janus kinase 2 in cytogenetically normal acute myeloid leukemia.
abstract: BACKGROUND
  Prognostic risk stratification according to acquired or inherited genetic alterations has received increasing attention in acute myeloid leukemia in recent years. A germline Janus kinase 2 haplotype designated as the 46/1 haplotype has been reported to be associated with an inherited predisposition to myeloproliferative neoplasms, and also to acute myeloid leukemia with normal karyotype. The aim of this study was to assess the prognostic impact of the 46/1 haplotype on disease characteristics and treatment outcome in acute myeloid leukemia.
  
  
  METHODS
  Janus kinase 2 rs12343867 single nucleotide polymorphism tagging the 46/1 haplotype was genotyped by LightCycler technology applying melting curve analysis with the hybridization probe detection format in 176 patients with acute myeloid leukemia under 60 years diagnosed consecutively and treated with curative intent.
  
  
  RESULTS
  The morphological subtype of acute myeloid leukemia with maturation was less frequent among 46/1 carriers than among non-carriers (5.6% versus 17.2%, P = 0.018, cytogenetically normal subgroup: 4.3% versus 20.6%, P = 0.031), while the morphological distribution shifted towards the myelomonocytoid form in 46/1 haplotype carriers (28.1% versus 14.9%, P = 0.044, cytogenetically normal subgroup: 34.0% versus 11.8%, P = 0.035). In cytogenetically normal cases of acute myeloid leukemia, the 46/1 carriers had a considerably lower remission rate (78.7% versus 94.1%, P = 0.064) and more deaths in remission or in aplasia caused by infections (46.8% versus 23.5%, P = 0.038), resulting in the 46/1 carriers having shorter disease-free survival and overall survival compared to the 46/1 non-carriers. In multivariate analysis, the 46/1 haplotype was an independent adverse prognostic factor for disease-free survival (P = 0.024) and overall survival (P = 0.024) in patients with a normal karyotype. Janus kinase 2 46/1 haplotype had no impact on prognosis in the subgroup with abnormal karyotype.
  
  
  CONCLUSIONS
  Janus kinase 2 46/1 haplotype influences morphological distribution, increasing the predisposition towards an acute myelomonocytoid form. It may be a novel, independent unfavorable risk factor in acute myeloid leukemia with a normal karyotype.
authors.affiliation: Department of Hematology and Stem Cell Transplantation, St Istvan and St Laszlo Hospital, Budapest, Hungary. nahajevszky@gmail.com
authors.forename: Sarolta
authors.initials: S
authors.lastname: Nahajevszky
authors.forename: Hajnalka
authors.initials: H
authors.lastname: Andrikovics
authors.forename: Arpad
authors.initials: A
authors.lastname: Batai
authors.forename: Emma
authors.initials: E
authors.lastname: Adam
authors.forename: Andras
authors.initials: A
authors.lastname: Bors
authors.forename: Judit
authors.initials: J
authors.lastname: Csomor
authors.forename: Laszlo
authors.initials: L
authors.lastname: Gopcsa
authors.forename: Magdalena
authors.initials: M
authors.lastname: Koszarska
authors.forename: Andras
authors.initials: A
authors.lastname: Kozma
authors.forename: Nora
authors.initials: N
authors.lastname: Lovas
authors.forename: Sandor
authors.initials: S
authors.lastname: Lueff
authors.forename: Zoltan
authors.initials: Z
authors.lastname: Matrai
authors.forename: Nora
authors.initials: N
authors.lastname: Meggyesi
authors.forename: Janos
authors.initials: J
authors.lastname: Sinko
authors.forename: Andrea
authors.initials: A
authors.lastname: Sipos
authors.forename: Andrea
authors.initials: A
authors.lastname: Varkonyi
authors.forename: Sandor
authors.initials: S
authors.lastname: Fekete
authors.forename: Attila
authors.initials: A
authors.lastname: Tordai
authors.forename: Tamas
authors.initials: T
authors.lastname: Masszi
mesh_terms: D000293:Adolescent; D000328:Adult; D018572:Disease-Free Survival; D005260:Female; D005500:Follow-Up Studies; D018095:Germ-Line Mutation; D006239:Haplotypes; D006801:Humans; D053614:Janus Kinase 2 / Q000235:genetics* / Q000378:metabolism; D059785:Karyotype; D015470:Leukemia, Myeloid, Acute / Q000175:diagnosis / Q000201:enzymology / Q000235:genetics* / Q000401:mortality*; D008297:Male; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide; D012307:Risk Factors; D015996:Survival Rate
chemical_list: C507924:JAK2 protein, human; D053614:Janus Kinase 2