Haematopoiesis

Biology

Polycythemia vera

Stem cell

Receptor

Myelofibrosis

Cancer research

Bone marrow

Janus kinase 2

Immunology

Genetics

Bioinformatics

Thrombocytosis

Cytokine

Ruxolitinib

Internal medicine

Medicine

Essential thrombocythemia

Janus kinase

Disease

Platelet

Blood

Myeloproliferative neoplasms (MPNs) are clonal hematopoietic stem cell disorders characterized by activated Janus kinase (JAK)–signal transducer and activator of transcription signaling. As a result, JAK inhibitors have been the standard therapy for treatment of patients with myelofibrosis (MF). Although currently approved JAK inhibitors successfully ameliorate MPN-related symptoms, they are not known to substantially alter the MF disease course. Similarly, in essential thrombocythemia and polycythemia vera, treatments are primarily aimed at reducing the risk of cardiovascular and thromboembolic complications, with a watchful waiting approach often used in patients who are considered to be at a lower risk for thrombosis. However, better understanding of MPN biology has led to the development of rationally designed therapies, with the goal of not only addressing disease complications but also potentially modifying disease course. We review the most recent data elucidating mechanisms of disease pathogenesis and highlight emerging therapies that target MPN on several biologic levels, including JAK2-mutant MPN stem cells, JAK and non-JAK signaling pathways, mutant calreticulin, and the inflammatory bone marrow microenvironment.

Biology and therapeutic targeting of molecular mechanisms in MPNs