AUTHOR=Jutzi Jonas Samuel , Mullally Ann
TITLE=Remodeling the Bone Marrow Microenvironment – A Proposal for Targeting Pro-inflammatory Contributors in MPN
JOURNAL=Frontiers in Immunology
VOLUME=11
YEAR=2020
URL=https://www.frontiersin.org/journals/immunology/articles/10.3389/fimmu.2020.02093
DOI=10.3389/fimmu.2020.02093
ISSN=1664-3224
ABSTRACT=
Philadelphia-negative myeloproliferative neoplasms (MPN) are malignant bone marrow (BM) 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 (MF) and highlights recent therapeutic advances. These findings outline the importance of malignant and non-malignant BM constituents to the pathogenesis and treatment of MF.