Genetics of Myeloproliferative Neoplasms

? Phenotypic driver mutations in JAK2, calreticulin, and MPL are present in 85% to 90% of myeloproliferative neoplasms and induce constitutive activation of JAK2-STAT signaling. ? Modern sequencing efforts have revealed large parts of the genomic landscape of myeloproliferative neoplasms with additional genetic alterations mainly in epigenetic modifiers and splicing factors. ? Genetic alterations in myeloproliferative neoplasms are subject to clonal evolution as myeloproliferative neoplasms progress, with high molecular risk mutations impacting dynamicsand outcome. ?Because JAK2 V617F is not specific to myeloproliferative neoplasms and is seen in other myeloid malignancies, it is important to note JAK2 V617F is recurrently detected in clonal hematopoiesisof indeterminate potential. ? The expanding insight into the genetic basis has facilitated diagnosis and prognostication of myeloproliferative neoplasms and poses novel candidates for targeted therapeutic