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1: Haematologica. 2008 Jan;93(1):34-40.Click here to read Links
Comment in:
Haematologica. 2008 Jan;93(1):4-6.

JAK2V617F mutation status identifies subtypes of refractory anemia with ringed sideroblasts associated with marked thrombocytosis.

Schmitt-Graeff AH, Teo SS, Olschewski M, Schaub F, Haxelmans S, Kirn A, Reinecke P, Germing U, Skoda RC.

Institute of Pathology, University Hospital, D-79108 Freiburg, Germany. annette.schmitt-graeff@gmx.de

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. DESIGN AND 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.

PMID: 18166783 [PubMed - indexed for MEDLINE]