Analysis of CALR-mutated essential thrombocythemia as a distinct disease entity compared with JAK2 V617F-mutated and triple-negative patients

Background/aim: Calreticulin (CALR) mutations in essential thrombocythemia (ET) are associated with younger age, higher platelet counts, and lower thrombosis rates. The present study analyzes the demographic, laboratory, and clinical features of the CALR mutation and its prognostic impact. Materials and methods: The clinical impact of CALR mutations was assessed in 391 ET patients. Results: CALR-mutation patients were more commonly male than JAK2 V617F-positive and triple-negative patients. Age at diagnosis was similar across all groups, although patients with type 2 CALR mutations were younger than those with nontype 1/nontype 2 mutations. Compared with JAK2 V617F-positive patients, CALR-mutation patients had lower leukocyte counts (9.6 × 10⁹/L vs. 10.9 × 10⁹/L), lower hemoglobin (Hb) and hematocrit (Hct) levels, higher platelet counts (1078.5 × 10⁹/L vs. 858.1 × 10⁹/L), and lower total thrombosis rates (20.8% vs. 37.8%), while the CALR-mutated and triple-negative patients had lower venous thrombosis rates than in the JAK2 V617F-positive patients. The arterial thrombosis rate before and at the time of diagnosis was lower in the CALR-mutation patients than in the JAK2 V617F-positive patients, and the total venous thrombosis rate in patients aged (CV) risk to be the only independent predictor of total thrombosis. Female gender, absence of CV risk, and platelet count ≥1000 × 10⁹/L were associated with a lower incidence of arterial thrombosis. Age Overall, thrombosis-free, and leukemia-free survival were similar across all groups, while myelofibrosis-free survival was longer in the type 2 CALR-mutation group. Conclusion: The CALR mutation was lower among females, and was associated with lower leukocyte counts, and Hb and Hct levels, and with higher platelet counts. In multivariable analysis, the apparent protective association of CALR with thrombosis was not independent.