CoChat
Sign Up
Cited by 2,003Myeloproliferative Neoplasms: Diagnosis and TreatmentAcute Myeloid Leukemia ResearchPlatelet Disorders and Treatments

The DOI matches its Crossref record; 32 of the 32 references it cites were found in a registry or an index.

Somatic Mutations of Calreticulin in Myeloproliferative Neoplasms

Open access
Klampfl, Thorsten, Gisslinger, Heinz, Harutyunyan, Ashot S., Nivarthi, Harini, Rumi, Elisa, Milosevic, Jelena D., Them, Nicole C.C., Berg, Tiina, Gisslinger, Bettina, Pietra, Daniela, Chen, Doris, Vladimer, Gregory I., Bagienski, Klaudia, Milanesi, Chiara, Casetti, Ilaria Carola, Sant'Antonio, Emanuela, Ferretti, Virginia, Elena, Chiara, Schischlik, Fiorella, Cleary, Ciara, Six, Melanie, Schalling, Martin, Schönegger, Andreas, Bock, Christoph, Malcovati, Luca, Pascutto, Cristiana, Superti-Furga, Giulio, Cazzola, Mario, Kralovics, Robert·2013·New England Journal of Medicine
DOI 10.1056/nejmoa1311347
Open this paper in CoChat — free accountOpen PDF

Abstract

BACKGROUND: Approximately 50 to 60% of patients with essential thrombocythemia or primary myelofibrosis carry a mutation in the Janus kinase 2 gene (JAK2), and an additional 5 to 10% have activating mutations in the thrombopoietin receptor gene (MPL). So far, no specific molecular marker has been identified in the remaining 30 to 45% of patients. METHODS: We performed whole-exome sequencing to identify somatically acquired mutations in six patients who had primary myelofibrosis without mutations in JAK2 or MPL. Resequencing of CALR, encoding calreticulin, was then performed in cohorts of patients with myeloid neoplasms. RESULTS: Somatic insertions or deletions in exon 9 of CALR were detected in all patients who underwent whole-exome sequencing. Resequencing in 1107 samples from patients with myeloproliferative neoplasms showed that CALR mutations were absent in polycythemia vera. In essential thrombocythemia and primary myelofibrosis, CALR mutations and JAK2 and MPL mutations were mutually exclusive. Among patients with essential thrombocythemia or primary myelofibrosis with nonmutated JAK2 or MPL, CALR mutations were detected in 67% of those with essential thrombocythemia and 88% of those with primary myelofibrosis. A total of 36 types of insertions or deletions were identified that all cause a frameshift to the same alternative reading frame and generate a novel C-terminal peptide in the mutant calreticulin. Overexpression of the most frequent CALR deletion caused cytokine-independent growth in vitro owing to the activation of signal transducer and activator of transcription 5 (STAT5) by means of an unknown mechanism. Patients with mutated CALR had a lower risk of thrombosis and longer overall survival than patients with mutated JAK2. CONCLUSIONS: Most patients with essential thrombocythemia or primary myelofibrosis that was not associated with a JAK2 or MPL alteration carried a somatic mutation in CALR. The clinical course in these patients was more indolent than that in patients with the JAK2 V617F mutation. (Funded by the MPN Research Foundation and Associazione Italiana per la Ricerca sul Cancro.).

Overview

The claims and statistics of this paper haven’t been checked yet.

Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.

A few free checks a day · papers already verified open instantly · results are public

Integrity signals

Registry

Crossref · 10.1056/nejmoa1311347

Cites

32 of 32 references verified0 citation errors · 0 not checkable

Statistics

Verification

Claims the paper makes

The claims and statistics of this paper haven’t been checked yet.

Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.

A few free checks a day · papers already verified open instantly · results are public

Claims other papers make about this one

Each is checked against this paper’s own text: does it say what the citing paper says it does?

Self-check

Percentages, sums and reported differences re-computed from the paper’s own numbers.

The self-check needs the paper’s full text.

Citations

Cites

Flagged first, then by citations

Show all 32 references

Cited by

Sorted by citations

Items 701–800 of 1,001

Related

See all

Metadata

Authors
Klampfl, T., Gisslinger, H., Harutyunyan, A. S., Nivarthi, H., Rumi, E., Milosevic, J. D., Them, N. C. C., Berg, T., Gisslinger, B., Pietra, D., Chen, D., Vladimer, G. I., Bagienski, K., Milanesi, C., Casetti, I. C., Sant'Antonio, E., Ferretti, V., Elena, C., Schischlik, F., Cleary, C., Six, M., Schalling, M., Schönegger, A., Bock, C., Malcovati, L., Pascutto, C., Superti-Furga, G., Cazzola, M., & Kralovics, R.
Affiliations
  • Austrian Academy of Sciences (AT)
  • Medical University of Vienna (AT)
  • Policlinico San Matteo Fondazione (IT)
  • University of Pavia (IT)
ORCID
Venue
New England Journal of Medicine
Publisher
Massachusetts Medical Society
Published
2013-12-19
Volume
369
Issue
25
Pages
2379-2390
ISSN
  • 0028-4793 (ISSN-L)
  • 1533-4406
DOI
10.1056/nejmoa1311347
OpenAlex
W2157694607
Cited by
2,003
References
32
Citations by year
2026: 80 · 2025: 63 · 2024: 81 · 2023: 117 · 2022: 122 · 2021: 173 · 2020: 144 · 2019: 146 · 2018: 153 · 2017: 200 · 2016: 247 · 2015: 243 · 2014: 222 · 2013: 7
FWCI
118.00
Type
journal article
Language
en
Open access
Locations
  • New England Journal of Medicine (publishedVersion)
  • PubMed (publishedVersion)
  • INFM-OAR (INFN Catania) (submittedVersion, other-oa)
Topics
  • Health Sciences › Medicine › Hematology › Myeloproliferative Neoplasms: Diagnosis and Treatment
  • Health Sciences › Medicine › Hematology › Acute Myeloid Leukemia Research
  • Health Sciences › Medicine › Hematology › Platelet Disorders and Treatments
Keywords
calreticulin, CALR mutation, myeloproliferative neoplasms, essential thrombocythemia, primary myelofibrosis, JAK2 V617F mutation, MPL mutation, somatic mutations, exon 9 deletion, frameshift mutation, STAT5 activation, thrombosis risk, overall survival
MeSH terms
Bone Marrow Diseases, Exons, Humans, Leukemia, Myeloid, Mutation, Thrombocythemia, Essential, Thrombosis, Proportional Hazards Models, Polymerase Chain Reaction, Sequence Analysis, DNA, Calreticulin, Janus Kinase 2, Receptors, Thrombopoietin, Primary Myelofibrosis

About these checks

Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.

Statistics and arithmetic are recomputed, not judged.

Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.

What counts as a claim ›How we measure confidence ›How we check this ›

Are you an author, or do you see a problem with this page? Request a review