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Updated: Mar 10, 2026

Engineering Oncogenic Heterozygous Gain-of-Function Mutations in Human Hematopoietic Stem and Progenitor Cells
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Mutant calreticulin-directed immunotherapies in myeloproliferative neoplasms

William L Heaton1, Matthew T Jenkins1, Nicole S Arellano1

  • 1Division of Hematology & Hematologic Malignancies, Huntsman Cancer Institute, University of Utah, Salt Lake City, UT.

Blood Neoplasia
|March 9, 2026
PubMed

Insights

Mutations in calreticulin (CALR) drive myeloproliferative neoplasms. Targeting the abnormal CALR protein with immunotherapy, including vaccines and T-cell therapies, shows promise for treatment.

Area of Science:

  • Oncology
  • Immunology
  • Hematology

Background:

  • Calreticulin (CALR) mutations are the second most frequent oncogenic drivers in myeloproliferative neoplasms (MPNs).
  • These mutations create a unique neomorphic C-terminal tail, absent in normal CALR, making it a potential target for immune system intervention.

Purpose of the Study:

  • To review the biology of normal and mutated calreticulin.
  • To summarize advancements in CALR-directed immunotherapies for MPNs.
  • To identify challenges and opportunities in clinical translation of these therapies.

Main Methods:

  • Literature review and synthesis of current research on CALR biology and immunotherapies.
  • Analysis of preclinical and early clinical data for CALR-targeted strategies.

Main Results:

  • Mutant CALR has been shown to elicit T-cell responses, validating it as a target.
  • Various immunotherapeutic approaches, including vaccines and T-cell therapies, are under development.

Conclusions:

  • CALR-directed immunotherapies represent a promising avenue for treating MPNs.
  • Further research and clinical trials are necessary to overcome challenges and translate these therapies into effective treatments.

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