Frequency of CALR mutations and correlation with laboratory findings and clinical outcome in Essential Thrombocythaemia and Primary Myelofibrosis patients
Julia Asp1,*, Ulrika Hansson2, Carina Wasslavik1, Peter Johansson3, Björn Andréasson3, Lars Palmqvist1
1Department of Clinical Chemistry and Transfusion Medicine, 2Department of Pathology, 3Haematology and Coagulation Section, the Sahlgrenska Academy, Göteborg, Sweden
Introduction: Somatic mutations in the Calreticulin gene CALR have recently been found in a large proportion of patients diagnosed with essential thrombocythaemia (ET) or primary myelofibrosis (PMF) negative for JAK2 or MPL mutations.
Objectives: The aim was to investigate the frequency of CALR mutations in ET and PMF patients and correlate this with laboratory findings and clinical outcome.
Methods: ET (n=145) and PMF (n=43) patients diagnosed according to the WHO 2008 classification between 2008 and 2013 in Western Sweden were investigated. Clinical and laboratory data including JAK2 and MPL mutation status was available. CALR mutation status was analysed with fragment analysis and Sanger sequencing.
Results: ET (n=47) and PMF (n=15) patients negative for the JAK2-V617F and MPL-W515 mutations were analysed for mutations in CALR exon 9. Of these, 62% and 47% were positive for CALR mutations respectively. CALR mutated ET cases (n=29) had significantly higher platelet counts (p=0.0005), more bone marrow fibrosis and fewer vascular complications (p=0.02 and p=0.03 respectively). JAK2-V617F mutated ET cases (n=95) had significantly higher haemoglobin and haematocrit values and lower EPO values (p=0.0005, p=0.0024 and p<0.0001 respectively). ET patients without JAK2, CALR or MPL mutations (n=18) had significantly more transformation to secondary myelofibrosis and acute myeloid leukaemia (p=0.02). No significant differences were seen between the different mutations in the PMF cases.
Conclusion: ET cases with CALR mutation have milder clinical course with less vascular complications in spite of higher platelet levels and more bone marrow fibrosis. ET cases with JAK2-V617F mutation have features similar to polycythaemia vera (PV), but without meeting the current diagnostic criteria for this disease. ET cases without JAK2, MPL or CALR mutations have increased risk of transformation to secondary myelofibrosis and acute myeloid leukaemia.
Keywords: Biomarker development, Blood