{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,3]],"date-time":"2026-06-03T10:33:26Z","timestamp":1780482806819,"version":"3.54.1"},"reference-count":22,"publisher":"MDPI AG","issue":"11","license":[{"start":{"date-parts":[[2022,10,23]],"date-time":"2022-10-23T00:00:00Z","timestamp":1666483200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100003725","name":"National Research Foundation of Korea","doi-asserted-by":"publisher","award":["2018R1D1A1B07051252"],"award-info":[{"award-number":["2018R1D1A1B07051252"]}],"id":[{"id":"10.13039\/501100003725","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Diagnostics"],"abstract":"<jats:p>Somatic CALR mutations occur in approximately 70% of patients with JAK2 V617F-negative essential thrombocythemia (ET) and primary myelofibrosis (PMF). We evaluated the effects of the CALR mutant type and burden on the phenotype of CALR-mutated myeloproliferative neoplasms (MPN). Of the 510 patients with suspected or diagnosed MPN, all 49 patients detected with CALR mutations were diagnosed with ET (n = 32) or PMF (n = 17). The CALR mutant burden was significantly higher in PMF than in ET (45% vs. 34%), and type 1-like and type 2-like mutations were detected in 49% and 51% patients, respectively. Patients with MPN and type 2-like mutation showed a significantly higher median platelet count than those with type 1-like mutation. Particularly, patients with ET and type 2-like mutation had no thrombotic events, despite higher platelet counts. The effect of CALR mutant burden differed depending on the mutant type. A higher mutant burden tended to be associated with a cytopenic phenotype (i.e., lower hemoglobin levels and platelet counts) in patients with the type 1-like mutation and a proliferative hematological phenotype (i.e., higher platelet and neutrophil counts) in patients with the type 2-like mutation. This study suggests that the disease phenotype of MPN may be altered through CALR mutant burden and mutant type.<\/jats:p>","DOI":"10.3390\/diagnostics12112570","type":"journal-article","created":{"date-parts":[[2022,10,24]],"date-time":"2022-10-24T02:31:03Z","timestamp":1666578663000},"page":"2570","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":9,"title":["Effects of CALR-Mutant Type and Burden on the Phenotype of Myeloproliferative Neoplasms"],"prefix":"10.3390","volume":"12","author":[{"given":"Hyun-Young","family":"Kim","sequence":"first","affiliation":[{"name":"Department of Laboratory Medicine and Genetics, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul 06351, Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3488-0881","authenticated-orcid":false,"given":"Yujin","family":"Han","sequence":"additional","affiliation":[{"name":"Department of Laboratory Medicine, Seegene Medical Foundation, Seoul 04805, Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jun Ho","family":"Jang","sequence":"additional","affiliation":[{"name":"Division of Hematology-Oncology, Department of Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul 06351, Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chul Won","family":"Jung","sequence":"additional","affiliation":[{"name":"Division of Hematology-Oncology, Department of Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul 06351, Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sun-Hee","family":"Kim","sequence":"additional","affiliation":[{"name":"Department of Laboratory Medicine and Genetics, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul 06351, Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hee-Jin","family":"Kim","sequence":"additional","affiliation":[{"name":"Department of Laboratory Medicine and Genetics, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul 06351, Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2022,10,23]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"651","DOI":"10.1042\/BJ20081847","article-title":"Calreticulin, a multi-process calcium-buffering chaperone of the endoplasmic reticulum","volume":"417","author":"Michalak","year":"2009","journal-title":"Biochem. J."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"2379","DOI":"10.1056\/NEJMoa1311347","article-title":"Somatic mutations of calreticulin in myeloproliferative neoplasms","volume":"369","author":"Klampfl","year":"2013","journal-title":"N. Engl. J. Med."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"2391","DOI":"10.1056\/NEJMoa1312542","article-title":"Somatic CALR mutations in myeloproliferative neoplasms with nonmutated JAK2","volume":"369","author":"Nangalia","year":"2013","journal-title":"N. Engl. J. Med."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"1552","DOI":"10.1182\/blood-2013-11-538983","article-title":"Impact of calreticulin mutations on clinical and hematological phenotype and outcome in essential thrombocythemia","volume":"123","author":"Rotunno","year":"2014","journal-title":"Blood"},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"1472","DOI":"10.1038\/leu.2014.3","article-title":"CALR vs JAK2 vs MPL-mutated or triple-negative myelofibrosis: Clinical, cytogenetic and molecular comparisons","volume":"28","author":"Tefferi","year":"2014","journal-title":"Leukemia"},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"431","DOI":"10.1038\/leu.2015.277","article-title":"Differential clinical effects of different mutation subtypes in CALR-mutant myeloproliferative neoplasms","volume":"30","author":"Pietra","year":"2016","journal-title":"Leukemia"},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"2465","DOI":"10.1182\/blood-2014-07-588426","article-title":"The prognostic advantage of calreticulin mutations in myelofibrosis might be confined to type 1 or type 1-like CALR variants","volume":"124","author":"Tefferi","year":"2014","journal-title":"Blood"},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"1568","DOI":"10.1038\/leu.2014.83","article-title":"Type 1 vs type 2 calreticulin mutations in primary myelofibrosis: Differences in phenotype and prognostic impact","volume":"28","author":"Tefferi","year":"2014","journal-title":"Leukemia"},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"249","DOI":"10.1038\/leu.2014.270","article-title":"Differential association of calreticulin type 1 and type 2 mutations with myelofibrosis and essential thrombocytemia: Relevance for disease evolution","volume":"29","author":"Cabagnols","year":"2015","journal-title":"Leukemia"},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"2391","DOI":"10.1182\/blood-2016-03-643544","article-title":"The 2016 revision to the World Health Organization classification of myeloid neoplasms and acute leukemia","volume":"127","author":"Arber","year":"2016","journal-title":"Blood"},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"1184","DOI":"10.3324\/haematol.2014.107482","article-title":"Distinct clinical characteristics of myeloproliferative neoplasms with calreticulin mutations","volume":"99","author":"Andrikovics","year":"2014","journal-title":"Haematologica"},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"1544","DOI":"10.1182\/blood-2013-11-539098","article-title":"JAK2 or CALR mutation status defines subtypes of essential thrombocythemia with substantially different clinical course and outcomes","volume":"123","author":"Rumi","year":"2014","journal-title":"Blood"},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"1317","DOI":"10.1182\/blood-2015-11-679571","article-title":"Calreticulin mutants in mice induce an MPL-dependent thrombocytosis with frequent progression to myelofibrosis","volume":"127","author":"Marty","year":"2016","journal-title":"Blood"},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"368","DOI":"10.1158\/2159-8290.CD-15-1434","article-title":"Mutant Calreticulin Requires Both Its Mutant C-terminus and the Thrombopoietin Receptor for Oncogenic Transformation","volume":"6","author":"Elf","year":"2016","journal-title":"Cancer Discov."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"508","DOI":"10.1111\/j.1600-0609.2007.00960.x","article-title":"The JAK2 V617F allele burden in essential thrombocythemia, polycythemia vera and primary myelofibrosis\u2014Impact on disease phenotype","volume":"79","author":"Larsen","year":"2007","journal-title":"Eur. J. Haematol."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"840","DOI":"10.1182\/blood-2006-12-064287","article-title":"Clinical profile of homozygous JAK2 617V>F mutation in patients with polycythemia vera or essential thrombocythemia","volume":"110","author":"Vannucchi","year":"2007","journal-title":"Blood"},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"1186","DOI":"10.1016\/j.exphem.2009.07.005","article-title":"JAK2(V617F) allele burden discriminates essential thrombocythemia from a subset of prefibrotic-stage primary myelofibrosis","volume":"37","author":"Hussein","year":"2009","journal-title":"Exp. Hematol."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"21","DOI":"10.1177\/2040620710394474","article-title":"JAK2 Allele Burden in the Myeloproliferative Neoplasms: Effects on Phenotype, Prognosis and Change with Treatment","volume":"2","author":"Vannucchi","year":"2011","journal-title":"Ther. Adv. Hematol."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"89","DOI":"10.1016\/j.hemonc.2016.04.003","article-title":"Integrating mutation variant allele frequency into clinical practice in myeloid malignancies","volume":"9","author":"Sallman","year":"2016","journal-title":"Hematol. Oncol. Stem. Cell Ther."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"510","DOI":"10.1016\/j.leukres.2015.02.006","article-title":"Frequency and allele burden of CALR mutations in Chinese with essential thrombocythemia and primary myelofibrosis without JAK2(V617F) or MPL mutations","volume":"39","author":"Li","year":"2015","journal-title":"Leuk. Res."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"42","DOI":"10.1016\/j.leukres.2017.12.005","article-title":"Quantitative assessment of JAK2 V617F and CALR mutations in Philadelphia negative myeloproliferative neoplasms","volume":"65","author":"Boha","year":"2018","journal-title":"Leuk. Res."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"1345","DOI":"10.1007\/s00277-021-04717-3","article-title":"Clinical effect of CALR allele burden in patients with essential thrombocythemia","volume":"101","author":"Bertozzi","year":"2022","journal-title":"Ann. Hematol."}],"container-title":["Diagnostics"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2075-4418\/12\/11\/2570\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T01:01:11Z","timestamp":1760144471000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2075-4418\/12\/11\/2570"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2022,10,23]]},"references-count":22,"journal-issue":{"issue":"11","published-online":{"date-parts":[[2022,11]]}},"alternative-id":["diagnostics12112570"],"URL":"https:\/\/doi.org\/10.3390\/diagnostics12112570","relation":{},"ISSN":["2075-4418"],"issn-type":[{"value":"2075-4418","type":"electronic"}],"subject":[],"published":{"date-parts":[[2022,10,23]]}}}