{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,13]],"date-time":"2026-10-13T16:35:23Z","timestamp":1791909323098,"version":"4.3.4"},"reference-count":21,"publisher":"Wiley","issue":"5","license":[{"start":{"date-parts":[[2015,12,13]],"date-time":"2015-12-13T00:00:00Z","timestamp":1449964800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/100001695","name":"International Waldenstrom's Macroglobulinemia Foundation","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100001695","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Br J Haematol"],"published-print":{"date-parts":[[2016,3]]},"abstract":"Summary<\/jats:title>CXCR<\/jats:styled-content>4<\/jats:italic>WHIM<\/jats:sup><\/jats:styled-content> somatic mutations are distinctive to Waldenstr\u00f6m Macroglobulinaemia (WM<\/jats:styled-content>), and impact disease presentation and treatment outcome. The clonal architecture of CXCR<\/jats:styled-content>4<\/jats:italic>WHIM<\/jats:sup><\/jats:styled-content> mutations remains to be delineated. We developed highly sensitive allele\u2010specific polymerase chain reaction (AS<\/jats:styled-content>\u2010PCR<\/jats:styled-content>) assays for detecting the most common CXCR<\/jats:styled-content>4<\/jats:italic>WHIM<\/jats:sup><\/jats:styled-content> mutations (CXCR<\/jats:styled-content>4<\/jats:italic>S338X C>A and C>G<\/jats:sup>) in WM<\/jats:styled-content>. The AS<\/jats:styled-content>\u2010PCR<\/jats:styled-content> assays detected CXCR<\/jats:styled-content>4<\/jats:italic>S338X<\/jats:sup> mutations in WM<\/jats:styled-content> and IgM monoclonal gammopathy of unknown significance (MGUS<\/jats:styled-content>) patients not revealed by Sanger sequencing. By combined AS<\/jats:styled-content>\u2010PCR<\/jats:styled-content> and Sanger sequencing, CXCR<\/jats:styled-content>4<\/jats:italic>WHIM<\/jats:sup><\/jats:styled-content> mutations were identified in 44\/102 (43%), 21\/62 (34%), 2\/12 (17%) and 1\/20 (5%) untreated WM<\/jats:styled-content>, previously treated WM<\/jats:styled-content>, IgM MGUS<\/jats:styled-content> and marginal zone lymphoma patients, respectively, but no chronic lymphocytic leukaemia, multiple myeloma, non\u2010IgM MGUS<\/jats:styled-content> patients or healthy donors. Cancer cell fraction analysis in WM<\/jats:styled-content> and IgM MGUS<\/jats:styled-content> patients showed CXCR<\/jats:styled-content>4<\/jats:italic>S338X<\/jats:sup> mutations were primarily subclonal, with highly variable clonal distribution (median 35\u00b71%, range 1\u00b72\u201397\u00b75%). Combined AS<\/jats:styled-content>\u2010PCR<\/jats:styled-content> and Sanger sequencing revealed multiple CXCR<\/jats:styled-content>4<\/jats:italic>WHIM<\/jats:sup><\/jats:styled-content> mutations in many individual WM<\/jats:styled-content> patients, including homozygous and compound heterozygous mutations validated by deep RNA<\/jats:styled-content> sequencing. The findings show that CXCR<\/jats:styled-content>4<\/jats:italic>WHIM<\/jats:sup><\/jats:styled-content> mutations are more common in WM<\/jats:styled-content> than previously revealed, and are primarily subclonal, supporting their acquisition after MYD<\/jats:styled-content>88L265P<\/jats:sup> in WM<\/jats:styled-content> oncogenesis. The presence of multiple CXCR<\/jats:styled-content>4<\/jats:italic>WHIM<\/jats:sup><\/jats:styled-content> mutations within individual WM<\/jats:styled-content> patients may be indicative of targeted CXCR<\/jats:styled-content>4 genomic instability.<\/jats:p>","DOI":"10.1111\/bjh.13897","type":"journal-article","created":{"date-parts":[[2015,12,14]],"date-time":"2015-12-14T03:58:45Z","timestamp":1450065525000},"page":"735-744","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":139,"title":["Clonal architecture of CXCR<\/scp>4 <\/i>WHIM<\/scp>\u2010like mutations in Waldenstr\u00f6m Macroglobulinaemia"],"prefix":"10.1111","volume":"172","author":[{"given":"Lian","family":"Xu","sequence":"first","affiliation":[{"name":"Bing Center for Waldenstr\u00f6m's Macroglobulinemia Dana Farber Cancer Institute Boston MA USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zachary 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