title: Clinical Manifestation of Calreticulin Gene Mutations in Essential Thrombocythemia without Janus Kinase 2 and MPL Mutations: A Chinese Cohort Clinical Study.
abstract: 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, JAK2V617F, and MPLW515 mutations by polymerase chain reaction and direct sequencing. We analyzed the relationship between the mutations and clinical features.
  
  
  RESULTS
  CALR, JAK2V617F, 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 del367fs46 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 CALR 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 with JAK2 mutant ET, CALR mutant ET showed a different clinical manifestation and an unfavorable prognosis. Thus, CALR is a potentially valuable diagnostic marker and therapeutic target in ET.
authors.affiliation: Department of Hematology, Affiliated Wuxi Peoples Hospital, Nanjing Medical University, Wuxi, Jiangsu 214023, China.
authors.forename: Chao
authors.initials: C
authors.lastname: Sun
authors.affiliation: Department of Hematology, Affiliated Wuxi Peoples Hospital, Nanjing Medical University, Wuxi, Jiangsu 214023, China.
authors.forename: Xin
authors.initials: X
authors.lastname: Zhou
authors.affiliation: Department of Hematology, Affiliated Wuxi Peoples Hospital, Nanjing Medical University, Wuxi, Jiangsu 214023, China.
authors.forename: Zhi-Jian
authors.initials: ZJ
authors.lastname: Zou
authors.affiliation: Department of Hematology, Affiliated Wuxi Peoples Hospital, Nanjing Medical University, Wuxi, Jiangsu 214023, China.
authors.forename: Hong-Feng
authors.initials: HF
authors.lastname: Guo
authors.affiliation: Department of Hematology, The First Affiliated Hospital of Nanjing Medical University, Jiangsu Province Hospital, Nanjing, Jiangsu 210029, China.
authors.forename: Jian-Yong
authors.initials: JY
authors.lastname: Li
authors.affiliation: Department of Hematology, The First Affiliated Hospital of Nanjing Medical University, Jiangsu Province Hospital, Nanjing, Jiangsu 210029, China.
authors.forename: Chun
authors.initials: C
authors.lastname: Qiao
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D044466:Asian People / Q000235:genetics; D015415:Biomarkers / Q000032:analysis; D037282:Calreticulin / Q000235:genetics*; D005260:Female; D006801:Humans; D053614:Janus Kinase 2 / Q000235:genetics*; D053208:Kaplan-Meier Estimate; D008297:Male; D008875:Middle Aged; D009154:Mutation; D053628:Receptors, Thrombopoietin / Q000235:genetics*; D013920:Thrombocythemia, Essential / Q000235:genetics* / Q000473:pathology; D013927:Thrombosis / Q000235:genetics; D055815:Young Adult
chemical_list: D015415:Biomarkers; C576483:CALR protein, human; D037282:Calreticulin; D053628:Receptors, Thrombopoietin; C082218:MPL protein, human; C507924:JAK2 protein, human; D053614:Janus Kinase 2