Tyrosine Kinase Inhibitors in the Treatment of Eosinophilic Neoplasms and Systemic Mastocytosis

Hematol Oncol Clin North Am. 2017 Aug;31(4):643-661. doi: 10.1016/j.hoc.2017.04.009.

Abstract

The World Health Organization's semimolecular classification of eosinophilias emphasizes neoplasms driven by fusion tyrosine kinases. More than 80% of patients with systemic mastocytosis carry the KIT D816V mutation, the primary driver of disease pathogenesis. Genetic annotation of these diseases is critical and affords opportunities for targeted therapy. This article discusses our understanding of the mutated tyrosine kinome of eosinophilic neoplasms and systemic mast cell disease, and the successes and limitations of available therapies. Use of tyrosine kinase inhibitors as a bridge to hematopoietic stem cell transplantation, and development of more selective and potent tyrosine kinase inhibitors is also highlighted.

Keywords: FGFR1; FIP1L1-PDGFRA; Hypereosinophilic syndrome; Imatinib; JAK2; Midostaurin; Systemic mastocytosis; Tyrosine kinase inhibitor.

Publication types

  • Review

MeSH terms

  • Algorithms
  • Antineoplastic Agents / pharmacology
  • Antineoplastic Agents / therapeutic use*
  • Disease Management
  • Enzyme Activation
  • Humans
  • Janus Kinases / metabolism
  • Mastocytosis, Systemic / diagnosis
  • Mastocytosis, Systemic / drug therapy*
  • Mastocytosis, Systemic / metabolism*
  • Mutation
  • Oncogene Proteins, Fusion / antagonists & inhibitors
  • Oncogene Proteins, Fusion / genetics
  • Oncogene Proteins, Fusion / metabolism
  • Protein Kinase Inhibitors / pharmacology
  • Protein Kinase Inhibitors / therapeutic use*
  • Protein-Tyrosine Kinases / antagonists & inhibitors*
  • Protein-Tyrosine Kinases / genetics
  • Protein-Tyrosine Kinases / metabolism
  • STAT Transcription Factors / metabolism
  • Signal Transduction / drug effects
  • Translocation, Genetic

Substances

  • Antineoplastic Agents
  • Oncogene Proteins, Fusion
  • Protein Kinase Inhibitors
  • STAT Transcription Factors
  • Protein-Tyrosine Kinases
  • Janus Kinases