title: JAK2V617F mutation status identifies subtypes of refractory anemia with ringed sideroblasts associated with marked thrombocytosis.
abstract: BACKGROUND
  Refractory anemia with ringed sideroblasts and marked thrombocytosis (RARS-T) was recently shown to be a JAK2-V617F mutation-related disorder. To determine the frequency and the prognostic significance of this mutation, we retrospectively evaluated 23 patients with platelet counts more than 600 x 10(9)/L, 15% ringed sideroblasts or more, and at least erythroid marrow dysplasia.
  
  
  METHODS
  An allele-specific polymerase chain reaction for JAK2-V617F was used to determine the allelic ratio of the mutated JAK2 allele in DNA samples extracted from bone marrow biopsies. Hematologic and survival data of the JAK2-V617F positive vs. the JAK2-V617F negative patients were statistically analyzed. Allele-specific polymerase chain reaction was also used to screen for MPL-W515 mutations.
  
  
  RESULTS
  The JAK2-V617F mutation was present in 11 patients (48%) and was associated with significantly higher erythrocyte and white blood cell counts (p=0.009 and 0.011, respectively). In 6/11 RARS-T patients the allelic ratio of JAK2-V617F was above 50%, indicating the presence of cells homozygous for the mutation. In two of these patients a transition from JAK2-V617F heterozygosity to homozygosity was documented and was accompanied by rising platelet counts in sequential samples. The MPL-W515L mutation was detected in one JAK2-V617F negative patient. The relative risk of death was found to be lower in the mutation-positive group than in the mutation-negative group.
  
  
  CONCLUSIONS
  RARS-T patients with JAK2-V617F have a more favorable prognosis than those without the JAK2 mutation. The prevalence of homozygous JAK2-V617F mutation in RARS-T suggests that this entity is biologically distinct from essential thrombocythemia.
authors.affiliation: Institute of Pathology, University Hospital, D-79108 Freiburg, Germany. annette.schmitt-graeff@gmx.de
authors.forename: Annette H
authors.initials: AH
authors.lastname: Schmitt-Graeff
authors.forename: Soon-Siong
authors.initials: SS
authors.lastname: Teo
authors.forename: Manfred
authors.initials: M
authors.lastname: Olschewski
authors.forename: Franz
authors.initials: F
authors.lastname: Schaub
authors.forename: Sabine
authors.initials: S
authors.lastname: Haxelmans
authors.forename: Andreas
authors.initials: A
authors.lastname: Kirn
authors.forename: Petra
authors.initials: P
authors.lastname: Reinecke
authors.forename: Ulrich
authors.initials: U
authors.lastname: Germing
authors.forename: Radek C
authors.initials: RC
authors.lastname: Skoda
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D000753:Anemia, Refractory / Q000235:genetics* / Q000378:metabolism; D000756:Anemia, Sideroblastic / Q000378:metabolism*; D004912:Erythrocytes / Q000166:cytology; D005260:Female; D005838:Genotype; D006720:Homozygote; D006801:Humans; D053614:Janus Kinase 2 / Q000096:biosynthesis / Q000235:genetics*; D008297:Male; D008875:Middle Aged; D009154:Mutation; D009190:Myelodysplastic Syndromes / Q000235:genetics*; D013922:Thrombocytosis / Q000235:genetics*
chemical_list: C507924:JAK2 protein, human; D053614:Janus Kinase 2