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Updated: Jan 18, 2026

Engineering Oncogenic Heterozygous Gain-of-Function Mutations in Human Hematopoietic Stem and Progenitor Cells
Published on: March 10, 2023
Mutant calreticulin in myeloproliferative neoplasms
Joan How1,2,3, Gabriela S Hobbs3, Ann Mullally1,2,4
1Division of Hematology, Department of Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, MA.
Abstract:
Recurrent mutations in calreticulin are present in ∼20% of patients with myeloproliferative neoplasms (MPNs). Since its discovery in 2013, we now have a more precise understanding of how mutant CALR, an endoplasmic reticulum chaperone protein, activates the JAK/STAT signaling pathway via a pathogenic binding interaction with the thrombopoietin receptor MPL to induce MPNs. In this Spotlight article, we review the current understanding of the biology underpinning mutant CALR-driven MPNs, discuss clinical implications, and highlight future therapeutic approaches.
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