Additional Genetic Alterations and Clonal Evolution of MPNs with Double Mutations on the MPL Gene: Two Case Reports.

Essential thrombocythemia (ET) and primary myelofibrosis (PMF) are two of the main -negative chronic myeloproliferative neoplasms (MPNs) characterized by abnormal megakaryocytic proliferation. () mutations are detected in 50-60% of ET and PMF, while () virus oncogene mutations are present in 3-5% of cases. While Sanger sequencing is a valuable diagnostic tool to discriminate the most common MPN mutations, next-generation sequencing (NGS) is a more sensitive technology that also identifies concurrent genetic alterations. In this report, we describe two MPN patients with simultaneous double mutations: a woman with ET presenting both and mutations and a man with PMF displaying an uncommon double . Using colony-forming assays and NGS analyses, we define the origin and mutational landscape of these two unusual malignancies and uncover further gene alterations that may contribute to the pathogenesis of ET and PMF.