title: Calreticulin mutation profile in Indian patients with primary myelofibrosis.
abstract: BACKGROUND
  Somatic mutations in Calreticulin (CALR) have been recently discovered in JAK2/MPL unmutated patients with primary myelofibrosis (PMF) or essential thrombocythemia.
  
  
  METHODS
  Clinical and hematologic features were obtained for 80 patients with PMF. JAK2V617F mutation was analyzed by DNA tetra-primer amplification refractory mutation system (ARMS-PCR). CALR and MPL mutations were identified by bi-directional Sanger sequencing.
  
  
  RESULTS
  CALR mutations were detected in 11.2% (9/80) of all PMF patients and 25.7% (9/35) of all JAK2V617F and MPL unmutated patients all of which were Type I mutation or deletions. A novel CALR mutation pattern (c.1241_1288del) was identified in one (1/9) patient. No case of Type II mutations or scattered point mutations was found in any of these patients. Uni-variate analysis at presentation showed that CALR mutations were significantly associated with younger age (P = 0.003) and larger spleen size (P = 0.001). No significant correlation was found between CALR mutation and clinico-hematologic characteristics or international prognostic scoring system (IPSS) scoring of the PMF patients.
  
  
  CONCLUSIONS
  CALR mutations have a distinct molecular profile in Indian patients, different from that of other studies worldwide. Larger prospective studies need to be designed to establish the impact of paucity of Type II mutations in contributing to disease phenotype and prognostic outcome of patients.
authors.forename: Sudha
authors.initials: S
authors.lastname: Sazawal
authors.forename: Neha
authors.initials: N
authors.lastname: Singh
authors.forename: Manoranjan
authors.initials: M
authors.lastname: Mahapatra
authors.forename: Renu
authors.initials: R
authors.lastname: Saxena
mesh_terms: D000328:Adult; D000368:Aged; D037282:Calreticulin / Q000235:genetics*; D015331:Cohort Studies; D004252:DNA Mutational Analysis; D005091:Exons; D005260:Female; D006801:Humans; D007194:India; D053614:Janus Kinase 2 / Q000235:genetics; D008297:Male; D008875:Middle Aged; D009154:Mutation; D055728:Primary Myelofibrosis / Q000175:diagnosis / Q000235:genetics*; D053628:Receptors, Thrombopoietin / Q000235:genetics
chemical_list: D037282:Calreticulin; D053628:Receptors, Thrombopoietin; C082218:MPL protein, human; D053614:Janus Kinase 2
keywords: ARMS-PCR; CALR mutation; Janus kinase-2 mutation; Primary myelofibrosis; Sanger sequencing