Type 1 calreticulin mutations in myeloproliferative neoplasms
Research type
Research Study
Full title
Development of an allele-specific PCR for detection and monitoring of type 1 CALR mutations in myeloproliferative neoplasms
IRAS ID
177456
Contact name
Donna Martin
Contact email
Sponsor organisation
University Hospitals Bristol NHS Foundation Trust
Duration of Study in the UK
0 years, 3 months, 1 days
Research summary
Myeloproliferative neoplasms (MPN) are cancers of the bone marrow that result in overproduction of the blood cells responsible for transport of oxygen, response to infection and normal blood clotting. If left untreated patients are at a high risk of death from blood clots, transformation into acute leukaemia or bone marrow scarring. Thus, it is extremely important to diagnose these conditions and differentiate them from other causes of overproduction of blood cells which do not require treatment.
Diagnosis of MPN has been transformed by the identification of specific genetic markers that accurately confirm the condition, including mutation of the JAK2 gene identified in 2005 and more recently, mutations in the calreticulin gene (CALR). The amount of mutation present (allele burden) has also been shown to alter symptoms, prognosis and test results of patients for the JAK2 mutation, though this is not yet fully investigated for CALR mutations.
Testing for JAK2 and CALR are now part of the diagnostic algorithm for patients presenting with features of MPN. The current method for detection of CALR mutations is a screening technique after which, positive samples are sent away for confirmation. This is expensive, time consuming (delaying diagnosis) and cannot assess the “allele burden”. We therefore propose to set up an “in-house” method for detection and quantification of type 1 CALR mutations (the most common form) and hope to correlate clinical features (blood counts, thrombosis, transformation to leukaemia or marrow scarring) with the results to generate some preliminary data regarding this.
The aims of this project are:
• Set up a sequence specific PCR assay for type 1 CALR mutations
• To compare the results of this test with the current method
• To compare allele burden results with patients clinical features
In the future, it is possible that results will help doctors make treatment decisions on patients.REC name
South West - Frenchay Research Ethics Committee
REC reference
15/SW/0121
Date of REC Opinion
18 Jun 2015
REC opinion
Further Information Favourable Opinion