Introduction: 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.
Conclusion: 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.
Keywords: ARMS-PCR; CALR mutation; Janus kinase-2 mutation; Primary myelofibrosis; Sanger sequencing.