ArticleLeukemia2023
CALR-mutated cells are vulnerable to combined inhibition of the proteasome and the endoplasmic reticulum stress response.
Article in Leukemia, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 19 papers.
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Who cites it
19 citing papers in PubMed, 23 citations in OpenAlex.
- Unfolded Protein Response Pathways in Cancer: Mechanisms, Tumor Biology and Therapeutic Opportunities.Molecular diagnosis & therapy · 2026Review
- Gene Expression Analysis of Mitochondria-Associated Membrane (MAM)-Related Genes in ER Stress and Alzheimer's Disease.Cellular and molecular neurobiology · 2026Article
- Endoplasmic reticulum stress in disease pathogenesis: its implications for therapy.Signal transduction and targeted therapy · 2026Review
- The interplay between autophagy and immunogenic cell death: nanomaterial-based strategies for cancer immunotherapy.Journal of nanobiotechnology · 2026Review
- Novel strategies targeting mutant calreticulin in essential thrombocythemia and myelofibrosis.Blood · 2026Review
- FDX1 is associated with CALR abundance and JAK-STAT-related inflammatory signaling in myeloproliferative neoplasms.Frontiers in oncology · 2026Article
- Challenges in the Evolving Role of Calreticulin as a Promising Target for Precision Medicine in Myeloproliferative Neoplasms.Cancers · 2025Review
- CALR Type 1-Like Mutations Increase Endoplasmic Reticulum Free CaCell biology international · 2025Article
- Development of a prognostic model for overall survival in neuroblastoma based on Schwann cell-specific genes, clinical predictors, and MYCN amplification.Translational cancer research · 2025Article
- Increased Complement C4 in a Sparse Neuronal Subset Induces Network-Wide Transcriptomic Alterations in the Prefrontal Cortex.bioRxiv : the preprint server for biology · 2025Article
- Differential regulation of mTORC2 signalling by type I and type II calreticulin (CALR) driver mutations of myeloproliferative neoplasm.Cell communication and signaling : CCS · 2025Article
- New approaches to standard of care in early-phase myeloproliferative neoplasms: can interferon-α alter the natural history of the disease?Haematologica · 2025Review
- Mutant Calreticulin in MPN: Mechanistic Insights and Therapeutic Implications.Current hematologic malignancy reports · 2025Review
- Rheumatoid arthritis-associated depression: focusing on the interactions between mitochondria and endoplasmic reticulum.Frontiers in pharmacology · 2025Review
- Lysosomal degradation targets mutant calreticulin and the thrombopoietin receptor in myeloproliferative neoplasms.Blood advances · 2024Article
- Platelet proteo-transcriptomic profiling validates mediators of thrombosis and proteostasis in patients with myeloproliferative neoplasms.bioRxiv : the preprint server for biology · 2023Article
- Review
- EBF1, MYO6 and CALR expression levels predict therapeutic response in diffuse large B-cell lymphomas.Frontiers in immunology · 2023Article
- Recent advances in therapies for primary myelofibrosis.Faculty reviews · 2023Review
Corrections and comments
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Authors and funding
15 authors at 7 institutions in 4 countries.
Funding
Abstract
Cancer is driven by somatic mutations that provide a fitness advantage. While targeted therapies often focus on the mutated gene or its direct downstream effectors, imbalances brought on by cell-state alterations may also confer unique vulnerabilities. In myeloproliferative neoplasms (MPN), somatic mutations in the calreticulin (CALR) gene are disease-initiating through aberrant binding of mutant CALR to the thrombopoietin receptor MPL and ligand-independent activation of JAK-STAT signaling. Despite these mechanistic insights into the pathogenesis of CALR-mutant MPN, there are currently no mutant CALR-selective therapies available. Here, we identified differential upregulation of unfolded proteins, the proteasome and the ER stress response in CALR-mutant hematopoietic stem cells (HSCs) and megakaryocyte progenitors. We further found that combined pharmacological inhibition of the proteasome and IRE1-XBP1 axis of the ER stress response preferentially targets Calr-mutated HSCs and megakaryocytic-lineage cells over wild-type cells in vivo, resulting in an amelioration of the MPN phenotype. In serial transplantation assays following combined proteasome/IRE1 inhibition for six weeks, we did not find preferential depletion of Calr-mutant long-term HSCs. Together, these findings leverage altered proteostasis in Calr-mutant MPN to identify combinatorial dependencies that may be targeted for therapeutic benefit and suggest that eradicating disease-propagating Calr-mutant LT-HSCs may require more sustained treatment.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.