SOHO State of the Art Updates and Next Questions: Myelofibrosis

Clin Lymphoma Myeloma Leuk. 2019 Apr;19(4):191-199. doi: 10.1016/j.clml.2019.03.011. Epub 2019 Mar 22.

Abstract

The discovery of a mutation in the Janus Kinase 2 gene in 2005 spurred significant progress in the field of myeloproliferative neoplasms. A comprehensive description of genomic factors at play in the malignant clone in myeloproliferative neoplasms, particularly myelofibrosis (MF), have recently led to more precise, personalized prognostic tools. Despite this, understanding of the disease pathogenesis remains relatively limited. We continue to lack a detailed description of the interaction between the hematopoietic stem cell clone, abnormal bone marrow niche cells, and circulating signaling molecules and an understanding of how they cooperate to promote cell proliferation, fibrogenesis, and extramedullary hematopoiesis. Despite our knowledge gaps, recent research in MF has led to promising clinical translation. In this article, we summarize recent insights into MF pathophysiology, progress in the development of novel therapeutics, and opportunities for further advancement of the field.

Keywords: Fibrosis; Inflammation; JAK inhibitors; MPN; Targeted therapy.

Publication types

  • Review

MeSH terms

  • Antineoplastic Agents / therapeutic use*
  • Biomarkers, Tumor / genetics
  • Biomarkers, Tumor / metabolism
  • Fibrosis
  • Hematopoiesis / drug effects
  • Humans
  • Janus Kinase 2 / antagonists & inhibitors
  • Janus Kinase 2 / genetics
  • Molecular Targeted Therapy / trends
  • Primary Myelofibrosis / drug therapy*
  • Primary Myelofibrosis / genetics
  • Primary Myelofibrosis / pathology
  • Primary Myelofibrosis / physiopathology*
  • Protein Kinase Inhibitors / therapeutic use
  • Signal Transduction / drug effects

Substances

  • Antineoplastic Agents
  • Biomarkers, Tumor
  • Protein Kinase Inhibitors
  • JAK2 protein, human
  • Janus Kinase 2