{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,23]],"date-time":"2026-10-23T22:38:47Z","timestamp":1792795127977,"version":"4.5.0"},"reference-count":67,"publisher":"Springer Science and Business Media LLC","license":[{"start":{"date-parts":[[2026,10,23]],"date-time":"2026-10-23T00:00:00Z","timestamp":1792713600000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2026,10,23]],"date-time":"2026-10-23T00:00:00Z","timestamp":1792713600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Bone Marrow Transplant"],"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>Myelofibrosis (MF), the most severe Philadelphia chromosome-negative myeloproliferative neoplasm, is driven by mutations in JAK2, CALR, or MPL, with CALR mutations accounting for 30\u201335% of cases. Mutant CALR forms an aberrant complex with the thrombopoietin receptor, resulting in constitutive JAK\u2013STAT signalling and is expressed on the malignant cell surface as a tumour-specific neoantigen absent from normal tissues, making it an attractive therapeutic target. Allogeneic haematopoietic cell transplantation (allo-HCT) remains the only curative treatment but is limited to selected patients with adequate fitness and a suitable donor. This review summarises the rapidly evolving landscape of CALR-directed therapies, including peptide vaccines, the Fc-silenced monoclonal antibody INCA033989, bispecific T-cell engagers, antibody-drug conjugates, and the CAR T-cell therapy RPG4, and explores their potential impact on transplant decision-making. INCA033989 has generated the most mature clinical data, demonstrating improvements in splenomegaly, constitutional symptoms, anaemia and early markers of disease modification, whereas cytotoxic approaches such as CAR T-cell therapy offer the prospect of deeper clonal eradication. Collectively, these therapies have the potential to redefine the role and timing of allo-HCT and expand treatment opportunities in the peri-transplant setting, including the targeted eradication of measurable residual disease following transplantation.<\/jats:p>","DOI":"10.1038\/s41409-026-03060-3","type":"journal-article","created":{"date-parts":[[2026,10,23]],"date-time":"2026-10-23T09:23:23Z","timestamp":1792747403000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["How could calreticulin-targeting therapies change the myelofibrosis transplant paradigm?"],"prefix":"10.1038","author":[{"ORCID":"https:\/\/orcid.org\/0009-0007-6510-5988","authenticated-orcid":false,"given":"Amy","family":"MacDonald","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Isaac","family":"Gannon","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Elena","family":"Torre","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9124-8981","authenticated-orcid":false,"given":"Trung","family":"Ngo","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jonathan","family":"Lambert","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Claire","family":"Roddie","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1224-091X","authenticated-orcid":false,"given":"Donal P.","family":"McLornan","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2681-5860","authenticated-orcid":false,"given":"Alexandros","family":"Rampotas","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2026,10,23]]},"reference":[{"key":"3060_CR1","doi-asserted-by":"publisher","first-page":"1200","DOI":"10.1182\/blood.2022015850","volume":"140","author":"DA Arber","year":"2022","unstructured":"Arber DA, Orazi A, Hasserjian RP, Borowitz MJ, Calvo KR, Kvasnicka HM, et al. 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