Clinical Manifestation of Calreticulin Gene Mutations in Essential Thrombocythemia without Janus Kinase 2 and MPL Mutations： A Chinese Cohort Clinical Study

Background： Recently, calreticulin （CALR） gene mutations have been identified in patients with essential thrombocythemia （ET）. A high-frequency of ET cases without Janus kinase 2 （JAK2） mutations contain CALR mutations and exhibit clinical characteristics different from those with mutant JAK2. Thus, we investigated the frequency and clinical features of Chinese patients of Han ethnicity with CALR mutations in ET. Methods： We recruited 310 Chinese patients of Han ethnicity with ET to analyze states of CALR, JAK2 V617F, and MPLW5 15 mutations by polymerase chain reaction and direct sequencing. We analyzed the relationship between the mutations and clinical features. Results： CALR, JAK2V617E and MPLW515 mutations were detected in 30% （n = 92）, 48% （n = 149）, and 1% （n = 4） of patients with ET, respectively. The mutation types of CALR involved deletion and insertion of base pairs. Most of them were Type 1 （52-bp deletion） and Type 2 （5-bp insertion, TTGTC） mutations, leading to de1367fs46 and ins385fs47, respectively. The three mutations were exclusive. Clinically, patients with mutated CALR had a lower hemoglobin level, lower white blood cell （WBC） count, and higher platelet count compared to those with mutated JAK2 （P 〈 0.05）. Furthermore, a significant difference was found in WBCs between wild-type patients （triple negative for JAK2, MPL, and CALR mutations） and patients with JAK2 mutations. Patients with CA LR mutations predominantly clustered into low or intermediate groups according to the International Prognostic Score of thrombosis for ET （P 〈 0.05）. Conclusions： CALR mutations were frequent in Chinese patients with ET, especially in those without JAK2 or MPL mutations. Compared withJAK2 mutant ET, CALR mutant ET showed a different clinical manifestation and an unfavorable prognosis. Thus, C4LR is a potentially valuable diagnostic marker and therapeutic target in ET.