Calreticulin Exon 9 Mutations in Myeloproliferative Neoplasms

Abstract

BackgroundCalreticulin (CALR) mutations were recently discovered in patients with myeloproliferative neoplasms (MPNs). We studied the frequency and type of CALR mutations and their hematological characteristics.MethodsA total of 168 MPN patients (36 polycythemia vera [PV], 114 essential thrombocythemia [ET], and 18 primary myelofibrosis [PMF] cases) were included in the study. CALR mutation was analyzed by the direct sequencing method.ResultsCALR mutations were detected in 21.9% of ET and 16.7% of PMF patients, which accounted for 58.5% and 33.3% of ET and PMF patients without Janus kinase 2 (JAK2) or myeloproliferative leukemia virus oncogenes (MPL) mutations, respectively. A total of five types of mutation were detected, among which, L367fs*46 (53.6%) and K385fs*47 (35.7%) were found to be the most common. ET patients with CALR mutation had lower leukocyte counts and ages compared with JAK2-mutated ET patients.ConclusionGenotyping for CALR could be a useful diagnostic tool for JAK2-or MPL-negative ET or PMF patients. CALR mutation may be a distinct disease group, with different hematological characteristics than that of JAK2-positive patients.

Frequency of Calreticulin (CALR) Mutation and Its Clinical Prognostic Significance in Essential Thrombocythemia and Primary Myelofibrosis: A Meta-analysis

“…CALR gene mutation has been reported to be closely associated with patients with PMF and ET (25,35). In the present meta-analysis (Fig.…”

CALR mutations screening in wild type JAK2V617F and MPLW515K/L Brazilian myeloproliferative neoplasm patients

“…Since CALR mutations discovery, several studies have been correlated these mutations with clinical data and patient outcome in MPN [14][15][16][17][18][19][20][21][22][23][24]. Interestingly, it was described the presence of CALR mutation in peripheral granulocytes of two PV patients negative for both JAK2 V617F and JAK2 exon12 mutations [25].…”

Coexisting JAK2V617F and CALR Exon 9 Mutation in Essential Thrombocythemia

“…It has been observed that phenotypic manifestations of CALR and JAK2V617F differ in ET and PMF that define subtypes with different prognosis [10,12,14,18,22] however comparatively the pathogenetic contribution of CALR/JAK2V617F double mutation is still unrevealed and it is not known if this would be another subgroup of MPN in future. The occurrence of JAK2V617F/CALR double mutants may be under-reported because many groups follow the initial findings of mutual exclusiveness for both genes [15].…”