{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,15]],"date-time":"2026-06-15T12:53:07Z","timestamp":1781527987635,"version":"3.54.1"},"reference-count":10,"publisher":"Wiley","issue":"11","license":[{"start":{"date-parts":[[2026,5,13]],"date-time":"2026-05-13T00:00:00Z","timestamp":1778630400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2026,5,13]],"date-time":"2026-05-13T00:00:00Z","timestamp":1778630400000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Clinical Laboratory Analysis"],"published-print":{"date-parts":[[2026,6]]},"abstract":"ABSTRACT<\/jats:title>\n \n Background<\/jats:title>\n \n Myeloproliferative neoplasms (MPNs) are clonal hematologic disorders commonly driven by mutations in\n JAK2<\/jats:italic>\n ,\n MPL<\/jats:italic>\n , or\n CALR<\/jats:italic>\n . Because routine CALR assays are largely optimized for the canonical Type 1 and Type 2 exon 9 variants, rare noncanonical mutations may be missed, creating diagnostic challenges.\n <\/jats:p>\n <\/jats:sec>\n \n Methods<\/jats:title>\n \n We report the case of a 78\u2010year\u2010old woman diagnosed with an MPN in 2016 and treated with hydroxyurea. Initial molecular testing included\n JAK2<\/jats:italic>\n V617F screening and PCR\u2010based fragment\u2010length analysis by capillary electrophoresis for\n CALR<\/jats:italic>\n exon 9 indels, both of which yielded negative results. After clinical progression, in 2024, repeat hematologic evaluation, bone marrow biopsy, Sanger sequencing, cloning, and next\u2010generation sequencing (NGS) were performed.\n <\/jats:p>\n <\/jats:sec>\n \n Results<\/jats:title>\n Disease progression was associated with marked thrombocytosis, leukocytosis, microcytic anemia, and bone marrow findings consistent with primary myelofibrosis. Advanced molecular testing identified a heterozygous CALR c.1122delG frameshift mutation (Type 26), a rare exon 9 variant not detected by the initial assay. Cloning confirmed heterozygosity, and NGS demonstrated a variant allele frequency of 43%. An additional CBL splice\u2010site mutation (VAF 17%) was also detected.<\/jats:p>\n <\/jats:sec>\n \n Conclusion<\/jats:title>\n This case highlights the limitations of routine assays focused on common CALR mutations and supports comprehensive sequencing\u2010based approaches for detecting rare CALR variants. Expanded molecular testing may improve diagnostic accuracy and clinical classification in MPNs.<\/jats:p>\n <\/jats:sec>","DOI":"10.1002\/jcla.70201","type":"journal-article","created":{"date-parts":[[2026,5,14]],"date-time":"2026-05-14T06:18:21Z","timestamp":1778739501000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Calreticulin Type 26 Mutation in Myelofibrosis: A Rare Variant With Diagnostic Challenges"],"prefix":"10.1002","volume":"40","author":[{"given":"Teresa","family":"Maltese","sequence":"first","affiliation":[{"name":"Division of Advanced Diagnostic Laboratories, Department of Clinical and Experimental Medicine University Hospital \u201cG. Martino\u201d Messina Messina Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Giuseppina","family":"Raffa","sequence":"additional","affiliation":[{"name":"Division of Advanced Diagnostic Laboratories, Department of Clinical and Experimental Medicine University Hospital \u201cG. Martino\u201d Messina Messina Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fabio","family":"Stagno","sequence":"additional","affiliation":[{"name":"Hematology Unit, Department of Human Pathology in Adulthood and Childhood \u201cGaetano Barresi\u201d University Hospital \u201cG. Martino\u201d Messina Messina Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rossana","family":"Leanza","sequence":"additional","affiliation":[{"name":"Hematology Unit, Department of Human Pathology in Adulthood and Childhood \u201cGaetano Barresi\u201d University Hospital \u201cG. Martino\u201d Messina Messina Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Paola","family":"Barone","sequence":"additional","affiliation":[{"name":"Hematology Unit, Department of Human Pathology in Adulthood and Childhood \u201cGaetano Barresi\u201d University Hospital \u201cG. Martino\u201d Messina Messina Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alessandro","family":"Allegra","sequence":"additional","affiliation":[{"name":"Hematology Unit, Department of Human Pathology in Adulthood and Childhood \u201cGaetano Barresi\u201d University Hospital \u201cG. Martino\u201d Messina Messina Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Teresa","family":"Pollicino","sequence":"additional","affiliation":[{"name":"Division of Advanced Diagnostic Laboratories, Department of Clinical and Experimental Medicine University Hospital \u201cG. Martino\u201d Messina Messina Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2026,5,13]]},"reference":[{"key":"e_1_2_5_2_1","doi-asserted-by":"publisher","DOI":"10.1002\/ajh.24221"},{"key":"e_1_2_5_3_1","doi-asserted-by":"publisher","DOI":"10.1111\/jcmm.17713"},{"key":"e_1_2_5_4_1","doi-asserted-by":"publisher","DOI":"10.1158\/2159\u20108290.CD\u201016\u20100238"},{"key":"e_1_2_5_5_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa1311347"},{"key":"e_1_2_5_6_1","doi-asserted-by":"publisher","DOI":"10.1097\/HS9.0000000000000333"},{"key":"e_1_2_5_7_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41375\u2010022\u201001613\u20101"},{"key":"e_1_2_5_8_1","doi-asserted-by":"publisher","DOI":"10.1111\/jcmm.17839"},{"key":"e_1_2_5_9_1","doi-asserted-by":"publisher","DOI":"10.1158\/2643\u20103230.BCD\u201021\u20100144"},{"key":"e_1_2_5_10_1","doi-asserted-by":"publisher","DOI":"10.1080\/09537104.2020.1869712"},{"issue":"2","key":"e_1_2_5_11_1","first-page":"7","article-title":"Basi Molecolari","volume":"5","author":"Guglielmelli P.","year":"2018","journal-title":"Ematologia Oncologica.it"}],"container-title":["Journal of Clinical Laboratory Analysis"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/jcla.70201","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/full-xml\/10.1002\/jcla.70201","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/jcla.70201","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,6,15]],"date-time":"2026-06-15T12:02:59Z","timestamp":1781524979000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1002\/jcla.70201"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,5,13]]},"references-count":10,"journal-issue":{"issue":"11","published-print":{"date-parts":[[2026,6]]}},"alternative-id":["10.1002\/jcla.70201"],"URL":"https:\/\/doi.org\/10.1002\/jcla.70201","archive":["Portico"],"relation":{},"ISSN":["0887-8013","1098-2825"],"issn-type":[{"value":"0887-8013","type":"print"},{"value":"1098-2825","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,5,13]]},"assertion":[{"value":"2025-03-04","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2026-03-08","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2026-05-13","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}],"article-number":"e70201"}}