Mutant calreticulin—Cancer driver and Achilles' heel for ET?

April 1, 2026HemaSphereOpen Access

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Key Points

The study aims to investigate the role of mutant calreticulin (mutCALR) in essential thrombocythemia (ET) and its implications for targeted therapies.
Examined the impact of mutCALR mutations on signaling pathways and platelet counts in patients with essential thrombocythemia.
Conducted clinical trials involving mutant calreticulin targeting therapies including monoclonal antibodies and T cell-engaging bispecific antibodies.
Evaluated patient outcomes, including hematological responses and molecular responses to mutCALR-targeting treatments.
Patients with type 1 mutCALR+ ET displayed better survival rates and higher platelet counts than JAK2V617F+ ET.
Early trials of mutCALR-targeted therapies showed over 90% of participants remained on the study after 12 months without dose-limiting toxicities.
Significant hematological responses were observed in ET patients, with a notable reduction in mutCALR variant allele frequency (VAF) after therapy.

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Explores the impact of mutant calreticulin on clinical outcomes in ET, suggesting novel immunotherapy pathways.

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Reichert et al. (2026) studied this question.

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