{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,13]],"date-time":"2026-10-13T16:35:58Z","timestamp":1791909358209,"version":"4.3.4"},"reference-count":30,"publisher":"Wiley","issue":"24","license":[{"start":{"date-parts":[[2024,12,23]],"date-time":"2024-12-23T00:00:00Z","timestamp":1734912000000},"content-version":"vor","delay-in-days":22,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Cancer Medicine"],"published-print":{"date-parts":[[2024,12]]},"abstract":"<jats:title>ABSTRACT<\/jats:title><jats:sec><jats:title>Background<\/jats:title><jats:p>Despite recurrent and activating mutations, including <jats:italic>MYD88<\/jats:italic>, <jats:italic>CXCR4<\/jats:italic>, <jats:italic>ARID1A<\/jats:italic>, <jats:italic>KMT2D<\/jats:italic>, and <jats:italic>CD79B<\/jats:italic> were identified, the genetic basis for Waldenstr\u00f6m's Macroglobulinemia (WM) and the risk of progression of IgM MGUS to WM remain to be fully elucidated.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>We investigated the mutation status of WM (<jats:italic>n<\/jats:italic>\u2009=\u20098), sWM (<jats:italic>n<\/jats:italic>\u2009=\u20097), and IgM MGUS (<jats:italic>n<\/jats:italic>\u2009=\u20095) patients, by performing high\u2010throughput targeted AmpliSeq NGS on 117 target genes. Specifically, we analyzed the CD19+ cells from 15 WM\/sWM patients and five IgM MGUS patients. We also analyzed the CD138+ cells from four WM\/sWM patients and two IgM MGUS patients.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>We detected the classic mutation <jats:italic>MYD88<\/jats:italic>L265P in 93% of WM\/sWM and in 60% of IgM MGUS patients. The <jats:italic>CXCR4<\/jats:italic>S338Ter mutation was identified in 26% of WM\/sWM patients, whereas it was undetectable in IgM MGUS subjects. Interestingly, we identified new mutated genes, including <jats:italic>WNK2<\/jats:italic> somatic mutations affecting 46% of WM\/sWM patients, for which a recurrent allelic variant (V1635Ter) was observed in this cohort. Moreover, sequencing evaluation revealed recurrently frameshift or missense mutations involving <jats:italic>NFKB2<\/jats:italic> (L473Afs) in 60% of IgM MGUS and 20% of WM\/sWM, <jats:italic>PTPN13<\/jats:italic> (P1546Tfs) in 20% of IgM MGUS and 7% of WM\/sWM, <jats:italic>CARD11<\/jats:italic> (S622del) in 20% of IgM MGUS and 20% of WM\/sWM, <jats:italic>KMT2C<\/jats:italic> (I823T) in all IgM MGUS and 93% of WM\/sWM, and <jats:italic>ATM<\/jats:italic> in 20% of IgM MGUS and 47% of WM\/sWM patients.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>In conclusion, we uncovered new insights into the mutational landscape of WM, depicting a more complex involvement of the NF\u2010kB pathway, and providing evidence of the recurrence of some variants (<jats:italic>MYD88<\/jats:italic>, <jats:italic>IL17RB<\/jats:italic>, <jats:italic>NFKB2<\/jats:italic>, <jats:italic>ATM<\/jats:italic>, <jats:italic>CARD11<\/jats:italic>, <jats:italic>PTPN13<\/jats:italic>, and <jats:italic>WNK2<\/jats:italic>) also in IgM MGUS.<\/jats:p><\/jats:sec>","DOI":"10.1002\/cam4.70525","type":"journal-article","created":{"date-parts":[[2024,12,23]],"date-time":"2024-12-23T08:10:13Z","timestamp":1734941413000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":5,"title":["Mutational Landscape of Bone Marrow <scp>CD19<\/scp> and <scp>CD138<\/scp> Cells in Waldenstr\u00f6m Macroglobulinemia (<scp>WM<\/scp>) and <scp>IgM<\/scp> Monoclonal Gammopathy of Undetermined Significance (<scp>IgM MGUS<\/scp>)"],"prefix":"10.1002","volume":"13","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-7659-2968","authenticated-orcid":false,"given":"Alessandra","family":"Trojani","sequence":"first","affiliation":[{"name":"Niguarda Hospital Department of Hematology and Oncology  Milano Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8234-3474","authenticated-orcid":false,"given":"Alessandro","family":"Beghini","sequence":"additional","affiliation":[{"name":"Department of Health Sciences University of Milano  Milano Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6409-8391","authenticated-orcid":false,"given":"Luca Emanuele","family":"Bossi","sequence":"additional","affiliation":[{"name":"Niguarda Hospital Department of Hematology and Oncology  Milano Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marta Rachele","family":"Stefanucci","sequence":"additional","affiliation":[{"name":"Niguarda Hospital Department of Hematology and Oncology  Milano Italy"},{"name":"Department of Health Sciences University of Milano  Milano Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Cassandra","family":"Palumbo","sequence":"additional","affiliation":[{"name":"Niguarda Hospital Department of Hematology and Oncology  Milano Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Antonino","family":"Greco","sequence":"additional","affiliation":[{"name":"A.R.N.A.S. Ospedali Civico Di Cristina Benfratelli  Palermo Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2587-7901","authenticated-orcid":false,"given":"Annamaria","family":"Frustaci","sequence":"additional","affiliation":[{"name":"Niguarda Hospital Department of Hematology and Oncology  Milano Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Barbara","family":"Di Camillo","sequence":"additional","affiliation":[{"name":"Department of Information Engineering University of Padova  Padova Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6372-2623","authenticated-orcid":false,"given":"Roberto","family":"Cairoli","sequence":"additional","affiliation":[{"name":"Niguarda Hospital Department of Hematology and Oncology  Milano Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2024,12,23]]},"reference":[{"key":"e_1_2_11_2_1","doi-asserted-by":"publisher","DOI":"10.1200\/JCO.19.02314"},{"key":"e_1_2_11_3_1","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2012-09-454355"},{"key":"e_1_2_11_4_1","doi-asserted-by":"publisher","DOI":"10.1038\/leu.2013.62"},{"key":"e_1_2_11_5_1","doi-asserted-by":"publisher","DOI":"10.1002\/ajh.26788"},{"key":"e_1_2_11_6_1","doi-asserted-by":"publisher","DOI":"10.3324\/haematol.2022.280953"},{"key":"e_1_2_11_7_1","doi-asserted-by":"publisher","DOI":"10.1111\/bjh.18502"},{"key":"e_1_2_11_8_1","doi-asserted-by":"publisher","DOI":"10.1158\/1078-0432.CCR-15-0646"},{"key":"e_1_2_11_9_1","doi-asserted-by":"publisher","DOI":"10.12688\/f1000research.12880.1"},{"key":"e_1_2_11_10_1","doi-asserted-by":"publisher","DOI":"10.1155\/2018\/6728128"},{"key":"e_1_2_11_11_1","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2017-01-761726"},{"key":"e_1_2_11_12_1","doi-asserted-by":"publisher","DOI":"10.3324\/haematol.2017.172718"},{"key":"e_1_2_11_13_1","doi-asserted-by":"publisher","DOI":"10.1038\/bcj.2017.72"},{"key":"e_1_2_11_14_1","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2016-03-708263"},{"key":"e_1_2_11_15_1","doi-asserted-by":"publisher","DOI":"10.1038\/sj.leu.2404520"},{"key":"e_1_2_11_16_1","doi-asserted-by":"publisher","DOI":"10.1038\/onc.2015.103"},{"key":"e_1_2_11_17_1","doi-asserted-by":"publisher","DOI":"10.3390\/cancers13081837"},{"key":"e_1_2_11_18_1","doi-asserted-by":"publisher","DOI":"10.2147\/OTT.S245950"},{"key":"e_1_2_11_19_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.isci.2022.104856"},{"key":"e_1_2_11_20_1","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2021.689472"},{"key":"e_1_2_11_21_1","doi-asserted-by":"publisher","DOI":"10.3389\/fonc.2020.591577"},{"key":"e_1_2_11_22_1","doi-asserted-by":"publisher","DOI":"10.1200\/JCO.2016.71.0814"},{"key":"e_1_2_11_23_1","doi-asserted-by":"publisher","DOI":"10.1136\/jclinpath-2019-206282"},{"key":"e_1_2_11_24_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.clml.2023.02.004"},{"key":"e_1_2_11_25_1","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2013-09-525808"},{"key":"e_1_2_11_26_1","doi-asserted-by":"publisher","DOI":"10.3390\/diagnostics12040969"},{"key":"e_1_2_11_27_1","doi-asserted-by":"publisher","DOI":"10.1002\/ajh.25600"},{"key":"e_1_2_11_28_1","doi-asserted-by":"publisher","DOI":"10.1158\/0008-5472.CAN-15-1022"},{"key":"e_1_2_11_29_1","doi-asserted-by":"crossref","unstructured":"M. L.Guerrera Z. R.Hunter K.Richardson et\u00a0al. \u201cAberrant Expression of Spliced WNK2 Is an Early Event in MYD88 Mutated WM That Activates ERK1\/2 and Supports Tumor Growth \u201d2023; Presented at: ASH2023 Congress; December 9\u201312 2023; San Diego CA USA and Online. 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