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Updated: Dec 9, 2025

Engineering Oncogenic Heterozygous Gain-of-Function Mutations in Human Hematopoietic Stem and Progenitor Cells
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Engineering Oncogenic Heterozygous Gain-of-Function Mutations in Human Hematopoietic Stem and Progenitor Cells

Published on: March 10, 2023

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[Mutant calreticulin and the molecular mechanisms in development of myeloproliferative neoplasms]

Marito Araki1

  • 1Department of Transfusion Medicine and Stem Cell Regulation, Juntendo University.

[Rinsho Ketsueki] the Japanese Journal of Clinical Hematology
|September 10, 2020
PubMed

Insights

Mutant calreticulin (CALR) drives myeloproliferative neoplasms (MPN) by forming complexes that activate the MPL receptor. Understanding this mechanism is key to MPN research.

Area of Science:

  • Molecular Biology
  • Oncology
  • Hematology

Background:

  • Myeloproliferative neoplasms (MPN) are a group of blood cancers.
  • A subset of Philadelphia chromosome-negative MPNs is associated with mutations in the calreticulin (CALR) gene.
  • Calreticulin acts as a molecular chaperone, but its mutant form has distinct oncogenic properties.

Purpose of the Study:

  • To evaluate the molecular mechanism of MPN development caused by mutant CALR.
  • To describe the discovery of this unique molecular mechanism.
  • To discuss future research directions for mutant CALR.

Main Methods:

  • Review of existing studies on mutant CALR and MPN.
  • Analysis of molecular interactions and signaling pathways.
  • Discussion of structural changes in mutant CALR.

Main Results:

  • Mutant CALR forms homomultimeric complexes through novel domains.
  • Mutant CALR exhibits high binding affinity for the MPL (thrombopoietin receptor).
  • Mutant CALR acts as an agonist, activating the MPL receptor.

Conclusions:

  • The discovery of mutant CALR's mechanism provides insight into MPN pathogenesis.
  • Further research into mutant CALR and MPL interactions is warranted.
  • This understanding may lead to targeted therapies for MPN.
Keywords:
CalreticulinJanus kinase 2Myeloproliferative neoplasmsThrombopoietin receptor

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