Calreticulin exon 9 mutations in myeloproliferative neoplasms

Ann Lab Med. 2015 Jan;35(1):22-7. doi: 10.3343/alm.2015.35.1.22. Epub 2014 Dec 8.

Abstract

Background: Calreticulin (CALR) mutations were recently discovered in patients with myeloproliferative neoplasms (MPNs). We studied the frequency and type of CALR mutations and their hematological characteristics.

Methods: A 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.

Results: CALR 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.

Conclusion: Genotyping 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.

Keywords: Calreticulin; JAK2; MPL; Myeloproliferative neoplasm.

MeSH terms

  • Adolescent
  • Adult
  • Aged
  • Aged, 80 and over
  • Amino Acid Sequence
  • Base Sequence
  • Calreticulin / genetics*
  • DNA Mutational Analysis
  • Exons
  • Female
  • Humans
  • Janus Kinase 2 / genetics
  • Leukocyte Count
  • Male
  • Middle Aged
  • Molecular Sequence Data
  • Mutation
  • Myeloproliferative Disorders / diagnosis
  • Myeloproliferative Disorders / genetics*
  • Myeloproliferative Disorders / pathology
  • Receptors, Thrombopoietin / genetics
  • Young Adult

Substances

  • Calreticulin
  • Receptors, Thrombopoietin
  • MPL protein, human
  • JAK2 protein, human
  • Janus Kinase 2