Primary myelofibrosis (PMF) is a chronic clonal myeloid disorder. Together with
essential thrombocythemia (ET) and
polycythemia vera (PV), it belongs to a group of
Philadelphia chromosome-negative myeloproliferative
neoplasms. An integral part of laboratory tests carried out in this disease group is detecting the presence of mutations in the
Janus kinase 2 gene at position 617 (JAK2 V617F) and in the gene encoding for the receptor for
thrombopoietin (myeloproliferative
leukemia virus oncogene, MPL) found in approximately 60% of PMF patients. The discovery of mutations affecting exon 9 of the
calreticulin (CALR) gene was of great benefit to the diagnosis of the diseases in JAK2 V617F and MPL unmutated cases. This is a study of the effect of a mutation in the CALR gene on the
clinical course in patients with primary, post-ET and post-PV
myelofibrosis. Analysis of 66 patients (54.5% JAK2 V617F; 34.8% CALR; 6.1% MPL; 3.0% triple negative; 1.5% coincidence of CALR and JAK2 V617F) confirmed a different phenotype of the disease in CALR-mutated patients as compared with CALR-unmutated individuals. Those with CALR mutation were significantly younger and had borderline higher platelet counts, less pronounced
splenomegaly and less frequent B symptoms at diagnosis. The study suggests that the driver mutation types define variations in the biological basis, clinical manifestations and course of the disease. The presence of CALR mutation has been shown to be an independent prognostic favorable factor. Careful risk stratification of these patients is of great importance to adequate therapeutic decision-making and
aids in selecting high-risk patients eligible for allogeneic
hematopoietic stem cell transplantation which continues to be the only treatment modality for
myelofibrosis having curative potential.