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Updated: Apr 7, 2026
Immunophenotyping and Cell Sorting of Human MKs from Human Primary Sources or Differentiated In Vitro from Hematopoietic Progenitors
Published on: August 7, 2021
Mastocytosis: a mutated KIT receptor induced myeloproliferative disorder
Anindya Chatterjee1, Joydeep Ghosh1,2, Reuben Kapur1,2,3,4
1Department of Pediatrics, Herman B Wells Center for Pediatric Research, Indiana University School of Medicine, Indianapolis, Indiana, USA.
Abstract:
Although more than 90% systemic mastocytosis (SM) patients express gain of function mutations in the KIT receptor, recent next generation sequencing has revealed the presence of several additional genetic and epigenetic mutations in a subset of these patients, which confer poor prognosis and inferior overall survival. A clear understanding of how genetic and epigenetic mutations cooperate in regulating the tremendous heterogeneity observed in these patients will be essential for designing effective treatment strategies for this complex disease. In this review, we describe the clinical heterogeneity observed in patients with mastocytosis, the nature of relatively novel mutations identified in these patients, therapeutic strategies to target molecules downstream from activating KIT receptor and finally we speculate on potential novel strategies to interfere with the function of not only the oncogenic KIT receptor but also epigenetic mutations seen in these patients.
Insights
Systemic mastocytosis (SM) involves KIT mutations, but additional genetic and epigenetic changes drive disease heterogeneity and poor survival. Understanding these mutations is key to developing new treatments for this complex blood disorder.
Area of Science:
- Hematology
- Oncology
- Genetics
Background:
- Systemic mastocytosis (SM) is characterized by abnormal mast cell proliferation.
- Over 90% of SM patients have activating mutations in the KIT receptor tyrosine kinase.
- Emerging evidence highlights additional genetic and epigenetic mutations contributing to disease complexity.
Purpose of the Study:
- To review the clinical heterogeneity in mastocytosis.
- To describe novel genetic and epigenetic mutations in SM.
- To discuss current and future therapeutic strategies targeting KIT and other mutations.
Main Methods:
- Literature review of clinical studies and next-generation sequencing data.
- Analysis of mutation profiles and their correlation with clinical outcomes.
- Exploration of targeted therapies and potential novel treatment approaches.
Main Results:
- Gain-of-function KIT mutations are prevalent in SM, but additional mutations significantly impact prognosis.
- These co-occurring mutations are associated with inferior overall survival.
- Understanding the interplay between genetic and epigenetic alterations is crucial for patient stratification.
Conclusions:
- The heterogeneity of SM is driven by a complex interplay of genetic and epigenetic mutations.
- Targeting not only the KIT receptor but also these additional mutations is essential for effective treatment.
- Further research into these cooperative mutations will pave the way for personalized therapeutic strategies in SM.
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