Category Ranking
98%
Total Visits
921
Avg Visit Duration
2 minutes
Citations
20
Article Abstract
Calreticulin (CALR) mutations are detected in around 20% of patients with primary and post-essential thrombocythemia myelofibrosis (MF). Regardless of driver mutations, patients with splenomegaly and symptoms are generally treated with JAK2-inhibitors, most commonly ruxolitinib. Recently, new therapies specifically targeting the CALR mutant clone have entered clinical investigation. To collect information on efficacy and safety of ruxolitinib in CALR-mutated patients, we report a sub-analysis of the "RUX-MF" (NCT06516406) study, comprising 135 CALR-mutated and 786 JAK2-mutated ruxolitinib-treated patients. Compared to JAK2-mutated patients, CALR-mutated patients started ruxolitinib with a more severe disease (higher peripheral blast counts, lower hemoglobin levels and worse marrow fibrosis) and after a longer median time from diagnosis (2.6 versus 0.7 years, p < 0.001). At 6 months, spleen responses were numerically inferior in CALR-mutated patients, who also had significantly lower rates of symptom responses (56.1% versus 66.7%, p = 0.04).
Download full-text PDF |
Source |
|---|---|
| http://www.ncbi.nlm.nih.gov/pmc/articles/PMC11868333 | PMC |
| http://dx.doi.org/10.1007/s00277-025-06204-5 | DOI Listing |
Publication Analysis
Top Keywords
Similar Publications
Novel Strategies Targeting Mutant Calreticulin in Essential Thrombocythemia and Myelofibrosis.
Blood
August 2025
Stanford University School of Medicine, Stanford, California, United States.
The discovery of calreticulin (CALR) mutations in patients with myeloproliferative neoplasms (MPN) has paved the way for the elucidation of a unique disease mechanism that is particularly well-suited to targeting by biologics. All MPN-associated pathogenic CALR mutations are characterized by a frameshift, resulting in translation of the same neoantigen peptide. This neoantigen directly activates the thrombopoietin receptor, leading to uncontrolled neoplastic cell proliferation.
View Article and Find Full Text PDFPNH clones prevalence study in ph-negative myeloproliferative neoplasms: a multicenter Italian study.
Ann Hematol
August 2025
U.O.C. di Ematologia, Ospedale di Ravenna e Università di Bologna, Ravenna, Italy.
The prevalence of paroxysmal nocturnal hemoglobinuria (PNH) clones is little investigated in myeloproliferative neoplasms (MPN) patients. The aim of this multicenter study was to evaluate the prevalence of PNH clones (glycosyl-phosphatidyl-inositol lacking) in 119 Ph- negative MPN patients having anemia, LDH elevation, asthenia and history of thrombosis. All the participating centers performed the standardized diagnostic test by using a single lyophilized template for granulocytes, monocytes, and erythrocytes.
View Article and Find Full Text PDFAssociation of the composition of the bone marrow tumor microenvironment in BCR::ABL1-negative myeloproliferative neoplasms with IFN-γ signaling and driver mutations.
Leukemia
August 2025
Institute of Pathology, University Hospital Halle, Martin Luther University Halle-Wittenberg, Halle (Saale), Germany.
Constitutive JAK/STAT pathway activation is crucial in the pathogenesis of BCR::ABL1-negative myeloproliferative neoplasms (MPN), but has not yet been linked to interferon (IFN)-γ signaling and tumor microenvironment. Human JAK2 V617F-mutated cell lines, 265 bone marrow biopsies (BMB) of two MPN cohorts, and 50 non-neoplastic BMB, revealed an intrinsic activation of IFN-γ signaling, which was confirmed by public RNA expression data. In vitro analysis of JAK2-mutated cell lines showed an activation of IFN-γ signaling pathway in the absence of IFN-γ in the cell supernatants.
View Article and Find Full Text PDFEssential thrombocythemia (ET) is a myeloproliferative neoplasm characterised by sustained thrombocytosis. Paradoxically, bleeding complications remain an under-recognised clinical challenge. Compared with CALR-mutated patients, those harbouring the JAK2-V617F variant appear more prone to haemorrhage.
View Article and Find Full Text PDFDNA methylation in primary myelofibrosis is partly associated with driver mutations and distinct from other myeloid malignancies.
Clin Epigenetics
May 2025
Institute for Stem Cell Biology, RWTH Aachen University Medical School, 52074, Aachen, Germany.
Background: Primary myelofibrosis (PMF) is a clonal blood disorder characterized by mutually exclusive driver mutations in JAK2, CALR, or MPL genes. So far, it is largely unclear if the driver mutations have a specific impact on DNA methylation (DNAm) profiles and how epigenetic alterations in PMF are related to other myeloid malignancies.
Results: When we compared DNAm profiles from PMF patients we found very similar epigenetic modifications in JAK2 and CALR mutated cases, whereas MPL mutations displayed less pronounced and distinct patterns.