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One of the greater success stories in this respect has been Waldenstr\u00f6m\u2019s Macroglobulinemia (WM), which is an incurable B-cell neoplasm characterized by serum monoclonal immunoglobulin M (IgM) and clonal lymphoplasmacytic cells infiltrating the bone marrow. Recent years have succeeded to describe the molecular landscape of WM in detail, highlighting two recurrently mutated genes, the\n                    <jats:italic>MYD88<\/jats:italic>\n                    and the\n                    <jats:italic>CXCR4<\/jats:italic>\n                    genes:\n                    <jats:italic>MYD88<\/jats:italic>\n                    with an almost constant and recurrent point mutation present in over 90% of patients and\n                    <jats:italic>CXCR4<\/jats:italic>\n                    with over 40 different mutations in the coding region affecting up to 40% of patients. Intriguingly, both mutations are activating mutations leading in the case of CXCR4 to an indelible activation and perpetual signaling of the chemokine receptor. These data have shed light on the essential role of CXCR4 in this disease and have paved the way to use these findings for predicting treatment response to the Bruton tyrosine kinase (BTK) inhibitor ibrutinib and novel therapeutic approaches in WM, which might be transferable to other related CXCR4 positive diseases. Well known for its central role in cancer progression and distribution, CXCR4 is highlighted in this review with regard to its biology, prognostic and predictive relevance and therapeutic implications in WM.\n                  <\/jats:p>","DOI":"10.1038\/s41375-020-01102-3","type":"journal-article","created":{"date-parts":[[2020,12,3]],"date-time":"2020-12-03T07:03:24Z","timestamp":1606979004000},"page":"333-345","update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":97,"title":["CXCR4 in Waldenstr\u00f6m\u2019s Macroglobulinema: chances and challenges"],"prefix":"10.1038","volume":"35","author":[{"given":"Lisa Marie","family":"Kaiser","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1689-1691","authenticated-orcid":false,"given":"Zachary R.","family":"Hunter","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Steven P.","family":"Treon","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9782-9012","authenticated-orcid":false,"given":"Christian","family":"Buske","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2020,12,3]]},"reference":[{"key":"1102_CR1","doi-asserted-by":"crossref","first-page":"271","DOI":"10.1016\/S0014-5793(98)00359-7","volume":"426","author":"A Caruz","year":"1998","unstructured":"Caruz A, Samsom M, Alonso JM, Alcami J, Baleux F, Virelizier JL, et al. 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N Engl J Med. 2018;378:2399\u2013410.","journal-title":"N Engl J Med"}],"container-title":["Leukemia"],"original-title":[],"language":"en","link":[{"URL":"http:\/\/www.nature.com\/articles\/s41375-020-01102-3.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"http:\/\/www.nature.com\/articles\/s41375-020-01102-3","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"http:\/\/www.nature.com\/articles\/s41375-020-01102-3.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2024,8,18]],"date-time":"2024-08-18T09:11:49Z","timestamp":1723972309000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.nature.com\/articles\/s41375-020-01102-3"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2020,12,3]]},"references-count":108,"journal-issue":{"issue":"2","published-print":{"date-parts":[[2021,2]]}},"alternative-id":["1102"],"URL":"https:\/\/doi.org\/10.1038\/s41375-020-01102-3","relation":{},"ISSN":["0887-6924","1476-5551"],"issn-type":[{"value":"0887-6924","type":"print"},{"value":"1476-5551","type":"electronic"}],"subject":[],"published":{"date-parts":[[2020,12,3]]},"assertion":[{"value":"13 August 2020","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"9 October 2020","order":2,"name":"revised","label":"Revised","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"17 November 2020","order":3,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"3 December 2020","order":4,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Compliance with ethical standards"}},{"value":"The authors declare the following competing interests: L.M.K. none; C.B. received honoraria from Roche, Pharmacyclics, Janssen, Beigene, AbbVie and received research funding from Roche, Janssen, MSD, Bayer. Z.M.H. holds an institutional patent issued for detection of CXCR4 mutations for diagnostic and treatment of WM; S.P.T. received research support from Pharmacyclics\/Abbvie, Bristol Myers Squibb, X4 Pharmaceuticals, Beigene and Eli Lilly as well as consultation fees from Pharmacyclics\/Abbvie, Janssen, and Beigene.","order":2,"name":"Ethics","group":{"name":"EthicsHeading","label":"Conflict of interest"}}]}}