Detection of driver and subclonal mutations in myelofibrosis : clinical impact on pharmacologic and transplant based treatment strategies

Myelofibrosis (MF) is the most aggressive form among Philadelphia negative (Ph-) myeloproliferative neoplasms (MPNs). In the last years, the mutational landscape of MF has expanded remarkably by the identification of additional recurrent mutations, called subclonal mutations. Areas covered: Here we describe the available data about the currently identified subclonal mutations and their prognostic value in MF patients. We also review the practical value of including such molecular information in available prognostic models for both outcome prediction and possibly treatment decision with regards to transplant indication. Lastly, we covered the available data on the application of molecular markers for minimal residual disease (MRD) monitoring after transplantation. Expert commentary: The demonstration of the prognostic value of additional mutations suggests to define this molecular profile at diagnosis and when an allogeneic transplant can be advised, particularly in younger patients. The presence of molecular markers might offer the possibility to evaluate the depth of remission and to monitor MRD after transplantation. Prospective clinical studies are needed to validate the use of this molecular data in the routine clinical practice.