EHA Library - The official digital education library of European Hematology Association (EHA)

Jan Samuelsson - Chair Introduction

The knowledge regarding the pathogenesis and prognosis of the classic Philadelphia
chromosome negative myeloproliferative neoplasms (MPN), that include polycythemia
vera (PV), essential thrombocythemia (ET) and primary myelofibrosis (PMF), has increased tremendously in the last 15 years. Since the discovery of the JAK2V617F mutation in 2005, additional mutations in JAK2 exon 12, as well as in the calreticulin and mpl genes have been identifed. In PMF, several additional non-driver mutations coupled with worse prognosis have also been delineated. The WHO classification of MPN:s from 2016 recognize the pathogenetic and clinical importance of these findings. The need for bone marrow assessment in the work-up of MPN patients is emphasized, an accurate diagnosis is an essential first step in the management of MPN. Important therapeutic progress has been made with the increased use of interferon-α in PV, as well as the introduction of JAK2 inhibitors both in PMF and PV. Despite a profound clinical benefit of these agents, further improvement is needed. Many of the above mentioned mutations represent potential targets for therapy, and may include type II JAK inhibitors, PI3 kinase inhibitors, immunotherapy against calreticulin, telomerase inhibition, recombinant human pentraxin-2 among others, or a combinatorial approach utilizing more than one agent.

Learning Objectives of the manuscript
After viewing this presentation the participant will be able to:
- To gain knowledge regarding the driver mutations that represent major diagnostic criteria for MPN in the revised 2016 WHO classification, as well as additional mutations associated with worse prognosis in PMF.
- To be able to use in daily clinical practice JAK2 inhibitors, interferon and other agents that have significantly advanced MPN treatment.
- To gain an insight into the fact that several avenues of research are being explored with the goal of improving the therapy of especially PMF patients including combination treatments with existing JAK inhibitors, developing mutant specific JAK2 inhibitors, and potentially immunological targeting of mutant CALR, as well as other avenues of treatment.

Learning Objectives of the presentation
After viewing this presentation the participant will be able to:
- Describe current status of mutation landscape in patients with myeloproliferative neoplasms (MPN).
- Describe the key role of driver mutations in the revised 2016 WHO diagnostic criteria of MPN.
- Discuss the prognostic relevance of driver and non-driver mutations for patients with myelofibrosis.