{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,13]],"date-time":"2026-10-13T16:35:25Z","timestamp":1791909325826,"version":"4.3.4"},"reference-count":37,"publisher":"Wiley","issue":"2","license":[{"start":{"date-parts":[[2022,10,9]],"date-time":"2022-10-09T00:00:00Z","timestamp":1665273600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100002704","name":"Fundaci\u00f3n Cient\u00edfica Asociaci\u00f3n Espa\u00f1ola Contra el C\u00e1ncer","doi-asserted-by":"publisher","award":["Lab_AECC2021"],"award-info":[{"award-number":["Lab_AECC2021"]}],"id":[{"id":"10.13039\/501100002704","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100005205","name":"Janssen Research and Development","doi-asserted-by":"publisher","award":["CP043186"],"award-info":[{"award-number":["CP043186"]}],"id":[{"id":"10.13039\/100005205","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100004587","name":"Instituto de Salud Carlos III","doi-asserted-by":"publisher","award":["PI19\/00669"],"award-info":[{"award-number":["PI19\/00669"]}],"id":[{"id":"10.13039\/501100004587","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100000780","name":"European Commission","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100000780","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":[[2023,1]]},"abstract":"<jats:title>Summary<\/jats:title><jats:p>Waldenstr\u00f6m macroglobulinaemia (WM) is characterized by recurrent somatic mutations in <jats:italic>MYD88<\/jats:italic> and <jats:italic>CXCR4<\/jats:italic> genes. However, limitations arise when analysing these mutations in IgM monoclonal gammopathy of undetermined significance (MGUS) or smouldering WM (SWM) given the lower tumour load. Here, we used droplet digital polymerase chain reaction (ddPCR) to analyse <jats:italic>MYD88<\/jats:italic> L265P and <jats:italic>CXCR4<\/jats:italic> S338* mutations (C1013G and C1013A) in unsorted bone marrow (BM) or cell\u2010free DNA (cfDNA) samples from 101 IgM MGUS and 69 SWM patients. ddPCR was more sensitive to assess <jats:italic>MYD88<\/jats:italic> L265P compared to allele\u2010specific PCR, especially in IgM MGUS (64% vs 39%). <jats:italic>MYD88<\/jats:italic> mutation burden correlated with other laboratory biomarkers, particularly BM infiltration (<jats:italic>r<\/jats:italic>\u00a0=\u00a00.8; <jats:italic>p<\/jats:italic>\u2009&lt;\u20090.001). <jats:italic>CXCR4<\/jats:italic> C1013G was analysed in <jats:italic>MYD88<\/jats:italic>\u2010mutated samples with available genomic DNA and was detected in 19\/54 (35%) and 18\/42 (43%) IgM MGUS and SWM cases respectively, also showing correlation with BM involvement (<jats:italic>r<\/jats:italic>\u00a0=\u00a00.9; <jats:italic>p<\/jats:italic>\u2009&lt;\u20090.001). ddPCR also detected 8 (38%) and 10 (63%) <jats:italic>MYD88<\/jats:italic>\u2010mutated cfDNA samples in IgM MGUS and SWM respectively. Moreover, high BM mutation burden (\u22658% <jats:italic>MYD88<\/jats:italic> and\u2009\u22652% <jats:italic>CXCR4<\/jats:italic>) was associated with an increased risk of progression to symptomatic WM. We show the clinical applicability of ddPCR to assess <jats:italic>MYD88<\/jats:italic> and <jats:italic>CXCR4<\/jats:italic> in IgM MGUS and SWM and provide a molecular\u2010based risk classification.<\/jats:p>","DOI":"10.1111\/bjh.18502","type":"journal-article","created":{"date-parts":[[2022,10,10]],"date-time":"2022-10-10T11:27:29Z","timestamp":1665401249000},"page":"187-196","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":30,"title":["Prognostic impact of <i><scp>MYD88<\/scp><\/i> and <i><scp>CXCR4<\/scp><\/i> mutations assessed by droplet digital polymerase chain reaction in <scp>IgM<\/scp> monoclonal gammopathy of undetermined significance and smouldering Waldenstr\u00f6m macroglobulinaemia"],"prefix":"10.1111","volume":"200","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-1752-3081","authenticated-orcid":false,"given":"David F.","family":"Moreno","sequence":"first","affiliation":[{"name":"Amyloidosis and Myeloma Unit, Department of Hematology Hospital Cl\u00ednic de Barcelona  Barcelona Spain"},{"name":"Institut d'Investigacions Biom\u00e8diques August Pi I Sunyer (IDIBAPS)  Barcelona Spain"},{"name":"Facultat de Medicina i Ci\u00e8ncies de la Salut Universitat de Barcelona (UB)  Barcelona Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"M\u00f3nica","family":"L\u00f3pez\u2010Guerra","sequence":"additional","affiliation":[{"name":"Institut d'Investigacions Biom\u00e8diques August Pi I Sunyer (IDIBAPS)  Barcelona Spain"},{"name":"Facultat de Medicina i Ci\u00e8ncies de la Salut Universitat de Barcelona (UB)  Barcelona Spain"},{"name":"Hematopathology Unit, Department of Pathology Hospital Cl\u00ednic de Barcelona  Barcelona Spain"},{"name":"Centro de Investigaci\u00f3n Biom\u00e9dica en Red de C\u00e1ncer (CIBERONC)  Madrid 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Cl\u00ednic de Barcelona  Barcelona Spain"},{"name":"Institut d'Investigacions Biom\u00e8diques August Pi I Sunyer (IDIBAPS)  Barcelona Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Juan G.","family":"Correa","sequence":"additional","affiliation":[{"name":"Amyloidosis and Myeloma Unit, Department of Hematology Hospital Cl\u00ednic de Barcelona  Barcelona Spain"},{"name":"Institut d'Investigacions Biom\u00e8diques August Pi I Sunyer (IDIBAPS)  Barcelona Spain"},{"name":"Facultat de Medicina i Ci\u00e8ncies de la Salut Universitat de Barcelona (UB)  Barcelona Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anthony M.","family":"Battram","sequence":"additional","affiliation":[{"name":"Amyloidosis and Myeloma Unit, Department of Hematology Hospital Cl\u00ednic de Barcelona  Barcelona Spain"},{"name":"Institut d'Investigacions Biom\u00e8diques August Pi I Sunyer (IDIBAPS)  Barcelona Spain"},{"name":"Facultat de Medicina i Ci\u00e8ncies de la Salut Universitat de Barcelona (UB)  Barcelona Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Miguel","family":"Osuna","sequence":"additional","affiliation":[{"name":"Institut d'Investigacions Biom\u00e8diques August Pi I Sunyer (IDIBAPS)  Barcelona Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0385-3415","authenticated-orcid":false,"given":"Alfredo","family":"Rivas\u2010Delgado","sequence":"additional","affiliation":[{"name":"Institut d'Investigacions Biom\u00e8diques August Pi I Sunyer (IDIBAPS)  Barcelona Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Luis Gerardo","family":"Rodr\u00edguez\u2010Lobato","sequence":"additional","affiliation":[{"name":"Amyloidosis and Myeloma Unit, Department of Hematology Hospital Cl\u00ednic de Barcelona  Barcelona Spain"},{"name":"Institut d'Investigacions Biom\u00e8diques August Pi I Sunyer (IDIBAPS)  Barcelona Spain"},{"name":"Facultat de 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(UB)  Barcelona Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Joan","family":"Blad\u00e9","sequence":"additional","affiliation":[{"name":"Amyloidosis and Myeloma Unit, Department of Hematology Hospital Cl\u00ednic de Barcelona  Barcelona Spain"},{"name":"Institut d'Investigacions Biom\u00e8diques August Pi I Sunyer (IDIBAPS)  Barcelona Spain"},{"name":"Facultat de Medicina i Ci\u00e8ncies de la Salut Universitat de Barcelona (UB)  Barcelona Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2534-9239","authenticated-orcid":false,"given":"Laura","family":"Rosi\u00f1ol","sequence":"additional","affiliation":[{"name":"Amyloidosis and Myeloma Unit, Department of Hematology Hospital Cl\u00ednic de Barcelona  Barcelona Spain"},{"name":"Institut d'Investigacions Biom\u00e8diques August Pi I Sunyer (IDIBAPS)  Barcelona Spain"},{"name":"Facultat de Medicina i Ci\u00e8ncies de la Salut Universitat de Barcelona (UB)  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