Mutations in myeloproliferative neoplasms - their significance and clinical use

Clonal hematologic diseases of the blood such as polycythemia vera, essential thrombocythemia and primary myelofibrosis belong to the BCR-ABL negative Myeloproliferative Neoplasms (MPN). These diseases are characterized by clonal expansion of hematopoietic precursor cells followed by increased production of differentiated cells of the myeloid lineage. Initiation of clonal hematopoiesis, formation of a clinical phenotype as well as disease progression form part of MPN disease evolution. The disease is driven by acquired somatic mutations in critical pathways such as cytokine signaling, epigenetic regulation, RNA splicing, and transcription factor signaling. Areas covered: The following review aims to provide an overview of the mutational landscape of MPN, the impact of these mutations in MPN pathogenesis as well as their prognostic value. Finally, a summary of how these mutations are being used or could potentially be used for the treatment of MPN patients is presented. Expert commentary: The genetic landscape of MPN patients has been successfully dissected within the past years with the advent of new sequencing technologies. Integrating the genetic information within a clinical setting is already benefitting patients in terms of disease monitoring and prognostic information of disease progression but will be further intensified within the next years.