Screening for calreticulin mutations in a cohort of patients suspected of having a myeloproliferative neoplasm

摘要

BACKGROUND. The discovery of calreticulin (CALR) has shown it to be the second most frequent mutation after the Janus Kinase 2 (JAK2) mutation in myeloproliferative neoplasms (MPNs). Its structure indicates various functions, of which two are to ensure calcium homeostasis and proper folding of other target proteins. Over 36 types of CALR mutations have been identified, all causing a recurrent frameshift in the C-terminal domain affecting CALR's localisation and calcium-binding function. OBJECTIVE. To screen a cohort of 89 patients suspected of having an MPN for the CALR mutations. METHODS. Capillary and gel electrophoresis were used in conjunction as confirmatory tests to screen the cohort of patients. RESULTS. Of three samples containing a type 1 CALR mutation, two were heterozygous and one homozygous for a 52-base pair deletion in CALR. CONCLUSIONS. Most studies report CALR mutations to be present only in patients with primary myelofibrosis or essential thrombocythaemia, with mutual exclusivity to JAK2 mutations. The findings of this study indicate that JAK2 and CALR mutations are no longer considered mutually exclusive. Similarly, patients with a polycythaemia vera phenotype could also carry a CALR mutation.