Remodeling the Bone Marrow Microenvironment – A Proposal for Targeting Pro-inflammatory Contributors in MPN
Jonas S. Jutzi, Ann Mullally
Abstract
Philadelphia-negative myeloproliferative neoplasms (MPN) are malignant bone marrow disorders, typically arising from a single somatically mutated hematopoietic stem cell. The most commonly mutated genes, JAK2, CALR and MPL lead to constitutively active JAK-STAT signaling. Common clinical features include myeloproliferation, splenomegaly and constitutional symptoms. This review covers the contributions of cellular components of MPN pathology (e.g. monocytes, megakaryocytes and mesenchymal stromal cells) as well as cytokines and soluble mediators to the development of myelofibrosis and highlights recent therapeutic advances. These findings outline the importance of malignant and non-malignant bone marrow constituents to the pathogenesis and treatment of myelofibrosis.