Effects of <i<CALR</i<-Mutant Type and Burden on the Phenotype of Myeloproliferative Neoplasms

Somatic <i<CALR</i< mutations occur in approximately 70% of patients with <i<JAK2</i< V617F-negative essential thrombocythemia (ET) and primary myelofibrosis (PMF). We evaluated the effects of the <i<CALR</i< mutant type and burden on the phenotype of <i<CAL...
Ausführliche Beschreibung

Somatic <i<CALR</i< mutations occur in approximately 70% of patients with <i<JAK2</i< V617F-negative essential thrombocythemia (ET) and primary myelofibrosis (PMF). We evaluated the effects of the <i<CALR</i< mutant type and burden on the phenotype of <i<CALR</i<-mutated myeloproliferative neoplasms (MPN). Of the 510 patients with suspected or diagnosed MPN, all 49 patients detected with <i<CALR</i< mutations were diagnosed with ET (n = 32) or PMF (n = 17). The <i<CALR</i< mutant burden was significantly higher in PMF than in ET (45% vs. 34%), and type 1-like and type 2-like mutations were detected in 49% and 51% patients, respectively. Patients with MPN and type 2-like mutation showed a significantly higher median platelet count than those with type 1-like mutation. Particularly, patients with ET and type 2-like mutation had no thrombotic events, despite higher platelet counts. The effect of <i<CALR</i< mutant burden differed depending on the mutant type. A higher mutant burden tended to be associated with a cytopenic phenotype (i.e., lower hemoglobin levels and platelet counts) in patients with the type 1-like mutation and a proliferative hematological phenotype (i.e., higher platelet and neutrophil counts) in patients with the type 2-like mutation. This study suggests that the disease phenotype of MPN may be altered through <i<CALR</i< mutant burden and mutant type. Ausführliche Beschreibung