{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,12]],"date-time":"2026-09-12T06:13:16Z","timestamp":1789193596129,"version":"build-2803163510"},"reference-count":26,"publisher":"Wiley","issue":"3","license":[{"start":{"date-parts":[[2026,6,18]],"date-time":"2026-06-18T00:00:00Z","timestamp":1781740800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"},{"start":{"date-parts":[[2026,6,18]],"date-time":"2026-06-18T00:00:00Z","timestamp":1781740800000},"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":["Br J Haematol"],"published-print":{"date-parts":[[2026,9]]},"abstract":"<jats:title>Summary<\/jats:title>\n                  <jats:p>\n                    Interpretation of rare non\u2010canonical\n                    <jats:italic>MPL<\/jats:italic>\n                    and\n                    <jats:italic>CALR<\/jats:italic>\n                    variants in myeloproliferative neoplasms (MPNs) remains challenging and frequently results in variants of uncertain significance (VUS). We explored whether these variants share structural or electrostatic features with established MPN driver mutations. We studied 179 patients with\n                    <jats:italic>BCR::ABL1<\/jats:italic>\n                    \u2010negative MPNs using targeted next\u2010generation sequencing (NGS), structural modelling, in silico pathogenicity assessment and unsupervised phenotypic clustering.\n                    <jats:italic>MPL<\/jats:italic>\n                    variants were mapped according to transmembrane helical orientation, while\n                    <jats:italic>CALR<\/jats:italic>\n                    exon 9 variants were evaluated according to predicted C\u2010terminal charge profiles. Eight patients (4.5%) harboured atypical molecular signatures, including non\u2010canonical\n                    <jats:italic>MPL<\/jats:italic>\n                    and\n                    <jats:italic>CALR<\/jats:italic>\n                    variants.\n                    <jats:italic>MPL<\/jats:italic>\n                    V501A mapped to the same transmembrane activation face as the canonical W515 hotspot, whereas\n                    <jats:italic>MPL<\/jats:italic>\n                    R592Q localized away from this region. Rare\n                    <jats:italic>CALR<\/jats:italic>\n                    34\u2010bp deletions generated positively charged C\u2010terminal tails similar to canonical pathogenic frameshifts, while a 12\u2010bp in\u2010frame deletion preserved the native acidic profile despite high variant allele frequency. Atypical cases showed clinical overlap with canonical MPN cohorts and clustered within related phenotypic groups on unsupervised analysis. Rare\n                    <jats:italic>MPL<\/jats:italic>\n                    and\n                    <jats:italic>CALR<\/jats:italic>\n                    variants may share structural and electrostatic features with established MPN drivers. Integrating receptor structure, charge effects and clinical phenotype may help contextualize atypical variants detected on routine NGS panels.\n                  <\/jats:p>","DOI":"10.1111\/bjh.70630","type":"journal-article","created":{"date-parts":[[2026,6,18]],"date-time":"2026-06-18T10:01:41Z","timestamp":1781776901000},"page":"978-987","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Resolving diagnostic uncertainty in rare\n                    <scp>\n                      <i>MPL<\/i>\n                    <\/scp>\n                    and\n                    <scp>CALR<\/scp>\n                    variants: A practical framework for the haematology clinic"],"prefix":"10.1111","volume":"209","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-2067-8567","authenticated-orcid":false,"given":"Suvir","family":"Singh","sequence":"first","affiliation":[{"name":"Dayanand Medical College and Hospital  Ludhiana India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Barjinderjit K","family":"Dhillon","sequence":"additional","affiliation":[{"name":"Dayanand Medical College and Hospital  Ludhiana India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Renu Moti","family":"Pandita","sequence":"additional","affiliation":[{"name":"Dayanand Medical College and Hospital  Ludhiana India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kunal","family":"Jain","sequence":"additional","affiliation":[{"name":"Dayanand Medical College and Hospital  Ludhiana India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jagdeep","family":"Singh","sequence":"additional","affiliation":[{"name":"Dayanand Medical College and Hospital  Ludhiana 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