Journal Article

Calreticulin mutations and long-term survival in essential thrombocythemia

Belachew, A A, Wolanskyj, A P, Finke, C, Lasho, T L, Wassie, E A, Hanson, C A, Ketterling, R P, Gangat, N, Tefferi, A, Pardanani, A

2014

Overview

The impact of calreticulin ( CALR ) mutations on long-term survival in essential thrombocythemia (ET) was examined in 299 patients whose diagnosis predated 2006. Mutational frequencies were 53% for Janus kinase 2 ( JAK2 ), 32% for CALR and 3% for MPL ; the remaining 12% were ‘triple-negative’. We confirmed the association of mutant CALR (vs JAK2 V617F) with younger age ( P =0.002), male sex ( P =0.01), higher platelet count (0.0004), lower hemoglobin ( P <0.0001), lower leukocyte count (0.02) and lower incidence of recurrent thrombosis (0.04). Triple-negative patients were also younger than their JAK2 -mutated counterparts ( P =0.003) and displayed lower hemoglobin ( P =0.003), lower leukocyte count (<0.0001) and lower thrombotic events ( P =0.02). Median follow-up time was 12.7 years and 47% of the patients were followed until death. Survival was the longest for triple-negative and shortest for MPL-mutated patients. Median survival was 19 years for JAK2 and 20 years for CALR-mutated cases ( P =0.32); the corresponding figures for patients of age ⩽65 years were 26 and 32 years ( P =0.56). The two mutational categories were also similar for leukemic ( P =0.28) and fibrotic ( P =0.28) progression rates. The current study is uniquely characterized by its very long follow-up period and provides accurate estimates of long-term survival in ET and complements current information on mutation-specific phenotype and prognosis.

• Publisher: Nature Publishing Group UK,Nature Publishing Group
• Subject: 692/699/1541/1990/2331 / Adolescent / Adult / Aged / Aged, 80 and over / Bone marrow / Calreticulin / Calreticulin - genetics / Cancer Research / Critical Care Medicine / Development and progression / Female / Follow-Up Studies / Gene mutations / Genetic aspects / Hematology / Hemoglobin / Humans / Intensive / Internal Medicine / Janus kinase / Janus kinase 2 / Janus Kinase 2 - genetics / Kinases / Laboratories / Lectins / Leukemia / Leukocytes / Male / Medical prognosis / Medicine / Medicine & Public Health / Middle Aged / Mutation / Oncology / original-article / Phenotypes / Prognosis / Properties / Receptors, Thrombopoietin - genetics / Survival / Survival analysis / Thrombocythemia / Thrombocythemia, Essential - complications / Thrombocythemia, Essential - diagnosis / Thrombocythemia, Essential - genetics / Thrombocythemia, Essential - mortality / Thrombocytosis / Thromboembolism / Thrombosis / Young Adult