KIT Mutations and Other Genetic Defects in Mastocytosis: Implications for Disease Pathology and Targeted Therapies

Immunol Allergy Clin North Am. 2023 Nov;43(4):651-664. doi: 10.1016/j.iac.2023.04.008. Epub 2023 Jun 11.

Abstract

A KIT activating mutation (usually KIT D816V) is detected in neoplastic cells in greater than 90% of indolent patients with systemic mastocytosis (SM). In more advanced variants of SM, additional genetic defects can be found in several myeloid malignancy-related genes, which can be detected by applying next-generation sequencing. Currently, the techniques recommended to detect the KIT D816V mutation and quantify the mutational burden in peripheral blood, bone marrow, or other organs/tissues are allele specific-quantitative PCR or droplet digital PCR. These techniques are useful for diagnosis, prognostication, follow-up and monitoring of therapeutic efficacy of cytoreductive agents in patients with SM.

Keywords: ASO-qPCR; KIT D816V mutation; Mast cells; Mastocytosis; Mutation burden; Tyrosine kinase inhibitors; ddPCR.

Publication types

  • Review
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Bone Marrow
  • Humans
  • Mast Cells
  • Mastocytosis* / diagnosis
  • Mastocytosis* / genetics
  • Mastocytosis* / therapy
  • Mastocytosis, Systemic* / diagnosis
  • Mastocytosis, Systemic* / drug therapy
  • Mastocytosis, Systemic* / genetics
  • Mutation
  • Proto-Oncogene Proteins c-kit / genetics

Substances

  • Proto-Oncogene Proteins c-kit