Remodeling the Bone Marrow Microenvironment - A Proposal for Targeting Pro-inflammatory Contributors in MPN

Front Immunol. 2020 Aug 31:11:2093. doi: 10.3389/fimmu.2020.02093. eCollection 2020.

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.

Keywords: CALR; JAK2; MPL; MPN; inflammation; megakaryocytes; mesenchymal stromal cells; monocytes.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Animals
  • Bone Marrow* / immunology
  • Bone Marrow* / pathology
  • Hematologic Neoplasms* / genetics
  • Hematologic Neoplasms* / immunology
  • Hematologic Neoplasms* / pathology
  • Humans
  • Mutation*
  • Myeloproliferative Disorders* / genetics
  • Myeloproliferative Disorders* / immunology
  • Myeloproliferative Disorders* / pathology
  • Neoplasm Proteins* / genetics
  • Neoplasm Proteins* / immunology
  • Signal Transduction* / genetics
  • Signal Transduction* / immunology
  • Tumor Microenvironment* / genetics
  • Tumor Microenvironment* / immunology

Substances

  • Neoplasm Proteins