ASH 2020 | Timing of driver mutations and clonal dynamics in MPNs: a new paradigm for blood cancer development

Jyoti Nangalia, MBBChir, Wellcome Sanger Institute, Hinxton, UK shares her excitement of the preliminary results of a project exploring the timing of driver mutations and clonal dynamics in adult myeloproliferative neoplasms (MPNs). Whole-genome sequencing of single-cell expansions from 10 patients with MPNs ranging from 20-70 years old revealed JAK2V617F and DNMT3A mutations were acquired very early in life, even in utero, despite the clinical presentation being over 30 years later. It was previously thought that aging promotes the outgrowth of these mutations, however, these results suggest the mutations occur very early on but evolve slowly throughout the lifetime of a patient. Additionally, clonal dynamics analysis revealed the clonal expansion rates positively correlate with disease presentation. Dr. Nangalia goes on to discuss how these findings could change the way MPNs are defined in the future and opens up the question of whether there could be such latencies between driver mutations and disease presentation of other blood neoplasms. This interview took place during the 62nd American Society of Hematology (ASH) Annual Meeting and Exposition, 2020.