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

• Published in: Diagnostics
• Main Authors: Hyun-Young Kim, Yujin Han, Jun Ho Jang, Chul Won Jung, Sun-Hee Kim, Hee-Jin Kim
• Format: Article
• Language: English
• Published: MDPI AG 2022-10-01
• Subjects: <i>CALR</i>; type 1 mutation; type 2 mutation; mutant burden; myeloproliferative neoplasm; essential thrombocythemia
• Online Access: https://www.mdpi.com/2075-4418/12/11/2570

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.