Molecular prognostication in Ph-negative MPNs in 2022

The application of genomic techniques, including cytogenetics and DNA sequencing, to decipher the molecular land-scape of patients with myeloproliferative neoplasms (MPNs) has radically modified diagnostic approach and man-agement through improved risk stratification. Three driver mutated genes (JAK2, MPL, CALR) are variably harbored by >80% of patients and associated with clinical characteristics, as well as major disease-related complications and different survival outcomes. Therefore, JAK2 V617F mutation is included in the revised International Prognosis Score of Thrombosis for Essential Thrombocythemia score for prediction of thrombosis in patients with essential throm-bocythemia and prefibrotic primary myelofi brosis, while a CALR type 1 mutated genotype constitutes a favorable variable for survival in patients with myelofibrosis (MF). Novel, integrated clinical and cytogenetic/ mutation scores (Mutation-Enhanced International Prognostic Score System for Transplantation-Age Patients with Primary Myelofi-brosis [MIPSS70 / v2], genetically inspired prognostic scoring system [GIPSS], Myelofibrosis Secondary to PV and ET-Prognostic Model [MYSEC -PM]) have been devised that guide selection of stem cell transplantation candidates with MF or help predict the risk associated with the transplant procedure (Myelofibrosis Transplant Scoring System), with greater performance compared with conventional scores based on hematologic and clinical variables only. On the other hand, several clinical needs remain unmet despite the great amount of molecular information avail able nowa-days. These include the prediction of evolution to acute leukemia in a clinically actionable time frame, the identifi-cation of patients most likely to derive durable benefits from target agents, in primis JAK inhibitors, and, conversely, the signifi cance of molecular responses that develop in patients receiving interferon or some novel agents. Here, we discuss briefly the signifi cance and the role of genomic analysis for prognostication in patients with MPNs from a clini-cian's point of view, with the intent to provide how-to-use hints.