title: Frequencies, clinical characteristics, and outcome of somatic  CALR mutations in JAK2-unmutated essential thrombocythemia.
abstract: Calreticulin (CALR) mutations were recently identified in patients with essential thrombocythemia (ET) and primary myelofibrosis (PMF) devoid of JAK2 and MPL mutations. We evaluated the clinical, laboratory, and molecular features of a Taiwanese population of patients with ET. Among 147 ET patients, CALR mutations were detected in 33 (22.5 %), JAK2V617F in 94 (63.9 %), and MPL mutations in 4 (2.7 %). Sixteen (10.9 %) patients were negative for all three mutations (CALR, JAK2V617F, and MPL; triple negative). Interestingly, one patient with the type 2 CALR mutation also harbored a low allele burden (0.025 %) of JAK2V617F mutation. Furthermore, we found a novel CALR mutation, with the resultant protein sharing an identical amino acid sequence to the type 6 CALR mutant. Compared to those with JAK2 mutation, CALR-mutated ET patients were characterized by younger age, lower leukocyte count, higher platelet count, and decreased risk of thrombosis. CALR mutations had a favorable impact on thrombosis-free survival (TFS) for ET patients, whereas the respective TFS outcomes were similarly poorer in JAK2-mutated ET and PV patients. Multivariate analysis confirmed that younger age (<60 years), presence of CALR mutations, and a lower platelet count (<1,000 × 10(9)/L) were independently associated with a longer TFS in ET patients. The current study demonstrates that CALR mutations characterize a special group of ET patients with unique phenotypes that are not discrepant from those seen in Western countries.
authors.forename: Chih-Cheng
authors.initials: CC
authors.lastname: Chen
authors.forename: Jyh-Pyng
authors.initials: JP
authors.lastname: Gau
authors.forename: Hui-Ju
authors.initials: HJ
authors.lastname: Chou
authors.forename: Jie-Yu
authors.initials: JY
authors.lastname: You
authors.forename: Cih-En
authors.initials: CE
authors.lastname: Huang
authors.forename: Yi-Yang
authors.initials: YY
authors.lastname: Chen
authors.forename: Jrhau
authors.initials: J
authors.lastname: Lung
authors.forename: Yi-Sheng
authors.initials: YS
authors.lastname: Chou
authors.forename: Yu-Wei
authors.initials: YW
authors.lastname: Leu
authors.forename: Chang-Hsien
authors.initials: CH
authors.lastname: Lu
authors.forename: Kuan-Der
authors.initials: KD
authors.lastname: Lee
authors.forename: Ying-Huang
authors.initials: YH
authors.lastname: Tsai
mesh_terms: D000328:Adult; D017677:Age Distribution; D000368:Aged; D000369:Aged, 80 and over; D000595:Amino Acid Sequence; D037282:Calreticulin / Q000235:genetics*; D005260:Female; D006801:Humans; D053614:Janus Kinase 2 / Q000235:genetics; D053208:Kaplan-Meier Estimate; D007958:Leukocyte Count; D008297:Male; D008875:Middle Aged; D008969:Molecular Sequence Data; D009154:Mutation; D010641:Phenotype; D010976:Platelet Count; D016016:Proportional Hazards Models; D053628:Receptors, Thrombopoietin / Q000235:genetics; D016415:Sequence Alignment; D017384:Sequence Deletion; D017386:Sequence Homology, Amino Acid; D013163:Splenomegaly / Q000209:etiology; D013624:Taiwan / Q000453:epidemiology; D013920:Thrombocythemia, Essential / Q000150:complications / Q000208:ethnology / Q000235:genetics* / Q000401:mortality; D019851:Thrombophilia / Q000209:etiology; D055815:Young Adult
chemical_list: C576483:CALR protein, human; D037282:Calreticulin; D053628:Receptors, Thrombopoietin; C082218:MPL protein, human; C507924:JAK2 protein, human; D053614:Janus Kinase 2