Myeloproliferative neoplasms

Learning goals

• Understand molecular mechanisms and importance of fibrosis in MPN.

• Recognise the importance and limitations of genomic analysis, and how disease biology relates to clinical phenotype.

• Know how patients with myelofibrosis should be managed, in particular which patients should be treated with ruxolitinib, approaches to control cytopenias and strategies for those who fail treatment.

Introduction

This session will focus on exciting new developments in our understanding of the processes that drive MPN and how this information is being translated into new treatments. The degree of fibrosis has been known for many years to be of prognostic significance in MPN. Ongoing studies are elucidating the mechanisms by which fibrosis develops, leading to the concept of a self-reinforcing malignant niche that is likely to require multiple therapeutic approaches to break down. Concerning the malignant clone itself, the spectrum of somatically acquired genomic lesions is generally well understood and includes variants that drive myeloproliferation, influence the clinical phenotype and promote disease progression. Although genetic analysis provides important diagnostic and prognostic information, it is clear that other factors such as ageing, inflammation and the bone marrow microenvironment also exert a significant influence on clonal dynamics. Finally, although targeted therapy with ruxolitinib is a cornerstone for treatment of intermediate/high risk patients with myelofibrosis, truly disease-modifying drugs or drug combinations remain to be identified. Combinations that influence the bone marrow microenvironment and/or address ruxolitinib-induced cytopenias are likely to be fruitful avenues for further investigation.