Analysis of Phenotype and Outcome in Essential Thrombocythemia with CALR or JAK2 mutations

The JAK2 V617F mutation, the thrombopoietin receptor MPL W515K/L mutation and the Calreticulin (CALR) mutations are mutually exclusive in essential thrombocythemia and support a novel molecular categorization of essential thrombocythemia. CALR mutations account for approximately 30 % of essential thrombocythemia cases. In a retrospective study, we have examined the frequency of MPL and CALR mutations in JAK2 V617F negative essential thrombocythemia (n=103). In addition, we compared the clinical phenotype and outcome of CALR mutant essential thrombocythemia with a cohort of JAK2 V617F positive essential thrombocythemia (n=57). CALR positive cases represented 63.7% of double negative essential thrombocythemia, and most carried CALR Type 1 or Type 2 indels. However, we also identified one patient, who was positive for both the JAK2 V617F and the CALR mutations. This study revealed that CALR mutant essential thrombocythemia is associated with younger age, higher platelet counts, lower erythrocyte counts, lower leukocyte counts, hemoglobin, hematocrit, and increased risk of progression to myelofibrosis in comparison with JAK2 V617F positive essential thrombocythemia. Analysis of the CALR mutant group according to indel type showed that CALR Type 1 deletion is strongly associated with male gender. CALR mutant patients had a better overall survival than JAK2 V617F positive patients, in particular patients of age 60 years or younger. In conclusion, this study on a Belgian cohort supports and extends the growing body of evidence that CALR mutant is phenotypically distinct from JAK2 V617F positive essential thrombocythemia, with regard to its clinical and hematological presentation as well as the overall survival.