{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,30]],"date-time":"2026-09-30T07:51:15Z","timestamp":1790754675770,"version":"4.1.0"},"reference-count":80,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2020,12,1]],"date-time":"2020-12-01T00:00:00Z","timestamp":1606780800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Immunol."],"abstract":"<jats:p>A highly recurrent somatic L265P mutation in the TIR domain of the signaling adapter MYD88 constitutively activates NF-\u03baB. It occurs in nearly all human patients with Waldenstr\u00f6m\u2019s macroglobulinemia (WM), a B cell malignancy caused by IgM-expressing cells. Here, we introduced an inducible leucine to proline point mutation into the mouse Myd88 locus, at the orthologous position L252P. When the mutation was introduced early during B cell development, B cells developed normally. However, IgM-expressing plasma cells accumulated with age in spleen and bone, leading to more than 20-fold elevated serum IgM titers. When introduced into germinal center B cells in the context of an immunization, the Myd88<jats:sup>L252P<\/jats:sup>mutation caused prolonged persistence of antigen-specific serum IgM and elevated numbers of antigen-specific IgM plasma cells. Myd88<jats:sup>L252P<\/jats:sup>-expressing B cells switched normally, but plasma cells expressing other immunoglobulin isotypes did not increase in numbers, implying that IgM expression may be required for the observed cellular expansion. In order to test whether the Myd88<jats:sup>L252P<\/jats:sup>mutation can cause clonal expansions, we introduced it into a small fraction of CD19-positive B cells. In this scenario, five out of five mice developed monoclonal IgM serum paraproteins accompanied by an expansion of clonally related plasma cells that expressed mostly hypermutated VDJ regions. Taken together, our data suggest that the Myd88<jats:sup>L252P<\/jats:sup>mutation is sufficient to promote aberrant survival and expansion of IgM-expressing plasma cells which in turn can cause IgM monoclonal gammopathy of undetermined significance (MGUS), the premalignant condition that precedes WM.<\/jats:p>","DOI":"10.3389\/fimmu.2020.602868","type":"journal-article","created":{"date-parts":[[2020,12,1]],"date-time":"2020-12-01T07:02:28Z","timestamp":1606806148000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":19,"title":["B-Cell-Specific Myd88 L252P Expression Causes a Premalignant Gammopathy Resembling IgM MGUS"],"prefix":"10.3389","volume":"11","author":[{"given":"Kristin","family":"Schmidt","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ulrike","family":"Sack","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Robin","family":"Graf","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wiebke","family":"Winkler","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Oliver","family":"Popp","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Philipp","family":"Mertins","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Thomas","family":"Sommermann","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christine","family":"Kocks","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Klaus","family":"Rajewsky","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2020,12,1]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","DOI":"10.1200\/jco.2000.18.1.214","article-title":"Waldenstr\u00f6m\u2019s Macroglobulinemia: Clinical Features, Complications, and Management","volume":"18","author":"Dimopoulos","year":"2000","journal-title":"J Clin Oncol"},{"key":"B2","doi-asserted-by":"publisher","DOI":"10.1053\/sonc.2003.50082","article-title":"Clinicopathological definition of Waldenstrom\u2019s macroglobulinemia: Consensus Panel Recommendations from the Second International Workshop on Waldenstrom\u2019s Macroglobulinemia","volume":"30","author":"Owen","year":"2003","journal-title":"Semin Oncol"},{"key":"B3","doi-asserted-by":"publisher","first-page":"77","DOI":"10.1111\/bjh.14196","article-title":"Recommendations for the diagnosis and initial evaluation of patients with Waldenstr\u00f6m Macroglobulinaemia: A Task Force from the 8th International Workshop on Waldenstr\u00f6m Macroglobulinaemia","volume":"175","author":"Castillo","year":"2016","journal-title":"Brit J Haematol"},{"key":"B4","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2016-01-643569","article-title":"The 2016 revision of the World Health Organization classification of lymphoid neoplasms","volume":"127","author":"Swerdlow","year":"2016","journal-title":"Blood"},{"key":"B5","doi-asserted-by":"publisher","DOI":"10.1182\/blood.2019000725","article-title":"How I treat Waldenstr\u00f6m macroglobulinemia","volume":"134","author":"Dimopoulos","year":"2019","journal-title":"Blood"},{"key":"B6","doi-asserted-by":"publisher","DOI":"10.1182\/blood.v97.1.321","article-title":"Clonal evolution in Waldenstrom macroglobulinemia highlights functional role of B-cell receptor","volume":"97","author":"Ciric","year":"2001","journal-title":"Blood"},{"key":"B7","doi-asserted-by":"publisher","DOI":"10.1182\/blood.V100.4.1505.h81602001505_1505_1507","article-title":"Typical Waldenstrom macroglobulinemia is derived from a B-cell arrested after cessation of somatic mutation but prior to isotype switch events","volume":"100","author":"Sahota","year":"2002","journal-title":"Blood"},{"key":"B8","doi-asserted-by":"publisher","DOI":"10.1053\/sonc.2003.50072","article-title":"Origins of the malignant clone in typical Waldenstrom\u2019s macroglobulinemia","volume":"30","author":"Sahota","year":"2003","journal-title":"Semin Oncol"},{"key":"B9","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2003-11-4024","article-title":"Clonotypic IgM V\/D\/J sequence analysis in Waldenstrom macroglobulinemia suggests an unusual B-cell origin and an expansion of polyclonal B cells in peripheral blood","volume":"104","author":"Kriangkum","year":"2004","journal-title":"Blood"},{"key":"B10","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1155\/2013\/815325","article-title":"Waldenstr\u00f6m Macroglobulinemia: Clinical and Immunological Aspects, Natural History, Cell of Origin, and Emerging Mouse Models","volume":"2013","author":"Janz","year":"2013","journal-title":"Isrn Hematol"},{"key":"B11","doi-asserted-by":"publisher","DOI":"10.3109\/10428194.2013.779689","article-title":"Clues to pathogenesis of Waldenstr\u00f6m macroglobulinemia and immunoglobulin M monoclonal gammopathy of undetermined significance provided by analysis of immunoglobulin heavy chain gene rearrangement and clustering of B-cell receptors","volume":"54","author":"Varettoni","year":"2013","journal-title":"Leukemia Lymphoma"},{"key":"B12","doi-asserted-by":"publisher","DOI":"10.1056\/nejmoa1200710","article-title":"MYD88 L265P Somatic Mutation in Waldenstr\u00f6m\u2019s Macroglobulinemia","volume":"367","author":"Treon","year":"2012","journal-title":"New Engl J Med"},{"key":"B13","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2014-05-573188","article-title":"Activation of lymphoma-associated MyD88 mutations via allostery-induced TIR-domain oligomerization","volume":"124","author":"Avbelj","year":"2014","journal-title":"Blood"},{"key":"B14","doi-asserted-by":"publisher","first-page":"97","DOI":"10.12703\/p6-97","article-title":"MyD88: a central player in innate immune signaling","volume":"6","author":"Deguine","year":"2014","journal-title":"F1000prime Rep"},{"key":"B15","doi-asserted-by":"publisher","first-page":"1785","DOI":"10.1038\/s41598-017-01998-5","article-title":"Clinicopathologic significance of MYD88 L265P mutation in diffuse large B-cell lymphoma: a meta-analysis","volume":"7","author":"Lee","year":"2017","journal-title":"Sci Rep UK"},{"key":"B16","doi-asserted-by":"publisher","DOI":"10.1038\/nature09671","article-title":"Oncogenically active MYD88 mutations in human lymphoma","volume":"470","author":"Ngo","year":"2011","journal-title":"Nature"},{"key":"B17","doi-asserted-by":"publisher","DOI":"10.1038\/s41586-018-0290-0","article-title":"A multiprotein supercomplex controlling oncogenic signalling in lymphoma","volume":"560","author":"Phelan","year":"2018","journal-title":"Nature"},{"key":"B18","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2012-12-475111","article-title":"A mutation in MYD88 (L265P) supports the survival of lymphoplasmacytic cells by activation of Bruton tyrosine kinase in Waldenstr\u00f6m macroglobulinemia","volume":"122","author":"Yang","year":"2013","journal-title":"Blood"},{"key":"B19","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2015-11-684183","article-title":"B-cell\u2013specific conditional expression of Myd88p.L252P leads to the development of diffuse large B-cell lymphoma in mice","volume":"127","author":"Knittel","year":"2016","journal-title":"Blood"},{"key":"B20","doi-asserted-by":"publisher","DOI":"10.1182\/bloodadvances.2019000588","article-title":"Human MYD88L265P is insufficient by itself to drive neoplastic transformation in mature mouse B cells","volume":"3","author":"Sewastianik","year":"2019","journal-title":"Blood Adv"},{"key":"B21","doi-asserted-by":"publisher","DOI":"10.1159\/000360992","article-title":"Outcome Disparities among Ethnic Subgroups of Waldenstr\u00f6m\u2019s Macroglobulinemia: A Population-Based Study","volume":"86","author":"Ailawadhi","year":"2014","journal-title":"Oncology"},{"key":"B22","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2011-10-384768","article-title":"Progression in smoldering Waldenstr\u00f6m macroglobulinemia: long-term results","volume":"119","author":"Kyle","year":"2012","journal-title":"Blood"},{"key":"B23","doi-asserted-by":"publisher","first-page":"2142","DOI":"10.12688\/f1000research.12880.1","article-title":"Advances in the understanding of IgM monoclonal gammopathy of undetermined significance","volume":"6","author":"Paludo","year":"2017","journal-title":"F1000research"},{"key":"B24","doi-asserted-by":"publisher","DOI":"10.1001\/jamaoncol.2016.5763","article-title":"Diagnosis and Management of Waldenstr\u00f6m Macroglobulinemia: Mayo Stratification of Macroglobulinemia and Risk-Adapted Therapy (mSMART) Guidelines 2016","volume":"3","author":"Kapoor","year":"2017","journal-title":"JAMA Oncol"},{"key":"B25","doi-asserted-by":"publisher","DOI":"10.1056\/nejmoa1709974","article-title":"Long-Term Follow-up of Monoclonal Gammopathy of Undetermined Significance","volume":"378","author":"Kyle","year":"2018","journal-title":"New Engl J Med"},{"key":"B26","doi-asserted-by":"publisher","DOI":"10.1002\/ajh.25292","article-title":"Waldenstr\u00f6m macroglobulinemia: 2019 update on diagnosis, risk stratification, and management","volume":"94","author":"Gertz","year":"2019","journal-title":"Am J Hematol"},{"key":"B27","doi-asserted-by":"publisher","DOI":"10.1038\/leu.2013.62","article-title":"MYD88 L265P is a marker highly characteristic of, but not restricted to, Waldenstr\u00f6m\u2019s macroglobulinemia","volume":"27","author":"Jim\u00e9nez","year":"2013","journal-title":"Leukemia"},{"key":"B28","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2012-06-436329","article-title":"MYD88 L265P mutation in Waldenstrom macroglobulinemia","volume":"121","author":"Poulain","year":"2013","journal-title":"Blood"},{"key":"B29","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2012-09-457101","article-title":"Prevalence and clinical significance of the MYD88 (L265P) somatic mutation in Waldenstr\u00f6m\u2019s macroglobulinemia and related lymphoid neoplasms","volume":"121","author":"Varettoni","year":"2013","journal-title":"Blood"},{"key":"B30","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2013-07-513366","article-title":"MYD88 (L265P) mutation is an independent risk factor for progression in patients with IgM monoclonal gammopathy of undetermined significance","volume":"122","author":"Varettoni","year":"2013","journal-title":"Blood"},{"key":"B31","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2012-09-454355","article-title":"MYD88 L265P in Waldenstr\u00f6m macroglobulinemia, immunoglobulin M monoclonal gammopathy, and other B-cell lymphoproliferative disorders using conventional and quantitative allele-specific polymerase chain reaction","volume":"121","author":"Xu","year":"2013","journal-title":"Blood"},{"key":"B32","doi-asserted-by":"publisher","DOI":"10.1038\/leu.2014.65","article-title":"Detection of MYD88 L265P in peripheral blood of patients with Waldenstr\u00f6m\u2019s Macroglobulinemia and IgM monoclonal gammopathy of undetermined significance","volume":"28","author":"Xu","year":"2014","journal-title":"Leukemia"},{"key":"B33","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0221941","article-title":"Detection of MYD88 L265P mutation by next-generation deep sequencing in peripheral blood mononuclear cells of Waldenstr\u00f6m\u2019s macroglobulinemia and IgM monoclonal gammopathy of undetermined significance","volume":"14","author":"Nakamura","year":"2019","journal-title":"PloS One"},{"key":"B34","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2014-03-564583","article-title":"C1013G\/CXCR4 acts as a driver mutation of tumor progression and modulator of drug resistance in lymphoplasmacytic lymphoma","volume":"123","author":"Roccaro","year":"2014","journal-title":"Blood"},{"key":"B35","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2014-01-550905","article-title":"Somatic mutations in MYD88 and CXCR4 are determinants of clinical presentation and overall survival in Waldenstr\u00f6m macroglobulinemia","volume":"123","author":"Treon","year":"2014","journal-title":"Blood"},{"key":"B36","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2013-09-525808","article-title":"The genomic landscape of Waldenstr\u00f6m macroglobulinemia is characterized by highly recurring MYD88 and WHIM-like CXCR4 mutations, and small somatic deletions associated with B-cell lymphomagenesis","volume":"123","author":"Hunter","year":"2014","journal-title":"Blood"},{"key":"B37","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2016-03-708263","article-title":"Transcriptome sequencing reveals a profile that corresponds to genomic variants in Waldenstr\u00f6m macroglobulinemia","volume":"128","author":"Hunter","year":"2016","journal-title":"Blood"},{"key":"B38","doi-asserted-by":"publisher","DOI":"10.1158\/1078-0432.ccr-15-0646","article-title":"Genomic Landscape of CXCR4 Mutations in Waldenstr\u00f6m Macroglobulinemia","volume":"22","author":"Poulain","year":"2016","journal-title":"Clin Cancer Res"},{"key":"B39","doi-asserted-by":"publisher","first-page":"795","DOI":"10.1111\/bjh.13361","article-title":"MYD88 L265P and CXCR4 mutations in lymphoplasmacytic lymphoma identify cases with high disease activity","volume":"169","author":"Schmidt","year":"2015","journal-title":"Brit J Haematol"},{"key":"B40","doi-asserted-by":"publisher","DOI":"10.1111\/bjh.13897","article-title":"Clonal architecture of CXCR4 WHIM-like mutations in Waldenstr\u00f6m Macroglobulinaemia","volume":"172","author":"Xu","year":"2016","journal-title":"Brit J Haematol"},{"key":"B41","doi-asserted-by":"publisher","DOI":"10.3324\/haematol.2017.172718","article-title":"Pattern of somatic mutations in patients with Waldenstr\u00f6m macroglobulinemia or IgM monoclonal gammopathy of undetermined significance","volume":"102","author":"Varettoni","year":"2017","journal-title":"Haematologica"},{"key":"B42","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.032068699","article-title":"Ability of the hydrophobic FGF and basic TAT peptides to promote cellular uptake of recombinant Cre recombinase: A tool for efficient genetic engineering of mammalian genomes","volume":"99","author":"Peitz","year":"2002","journal-title":"Proc Natl Acad Sci"},{"key":"B43","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1516428112","article-title":"The B-cell antigen receptor integrates adaptive and innate immune signals","volume":"112","author":"Otipoby","year":"2015","journal-title":"Proc Natl Acad Sci"},{"key":"B44","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.0602353103","article-title":"Tracking germinal center B cells expressing germ-line immunoglobulin \u03b31 transcripts by conditional gene targeting","volume":"103","author":"Casola","year":"2006","journal-title":"Proc Natl Acad Sci"},{"key":"B45","doi-asserted-by":"publisher","first-page":"4","DOI":"10.1186\/1471-213x-1-4","article-title":"Cre reporter strains produced by targeted insertion of EYFP and ECFP into the ROSA26 locus","volume":"1","author":"Srinivas","year":"2001","journal-title":"BMC Dev Biol"},{"key":"B46","doi-asserted-by":"publisher","DOI":"10.1093\/nar\/25.6.1317","article-title":"B Lymphocyte-Specific, Cre-mediated Mutagenesis in Mice","volume":"25","author":"Rickert","year":"1997","journal-title":"Nucleic Acids Res"},{"key":"B47","doi-asserted-by":"publisher","DOI":"10.1101\/sqb.2013.78.020222","article-title":"Studying Epstein\u2013Barr Virus Pathologies and Immune Surveillance by Reconstructing EBV Infection in Mice","volume":"78","author":"Yasuda","year":"2013","journal-title":"Cold Spring Harb Sym"},{"key":"B48","doi-asserted-by":"publisher","DOI":"10.1002\/1521-4141(200211)32:11<3152::aid-immu3152>3.0.co;2-2","article-title":"DNA polymerase \u03ba deficiency does not affect somatic hypermutation in mice","volume":"32","author":"Schenten","year":"2002","journal-title":"Eur J Immunol"},{"key":"B49","doi-asserted-by":"publisher","DOI":"10.1093\/nar\/gkt382","article-title":"IgBLAST: an immunoglobulin variable domain sequence analysis tool","volume":"41","author":"Ye","year":"2013","journal-title":"Nucleic Acids Res"},{"key":"B50","doi-asserted-by":"publisher","first-page":"55","DOI":"10.1016\/s0145-305x(02)00039-3","article-title":"IMGT unique numbering for immunoglobulin and T cell receptor variable domains and Ig superfamily V-like domains","volume":"27","author":"Lefranc","year":"2003","journal-title":"Dev Comp Immunol"},{"key":"B51","doi-asserted-by":"publisher","DOI":"10.1038\/nprot.2006.468","article-title":"In-gel digestion for mass spectrometric characterization of proteins and proteomes","volume":"1","author":"Shevchenko","year":"2006","journal-title":"Nat Protoc"},{"key":"B52","doi-asserted-by":"publisher","DOI":"10.1038\/nprot.2007.261","article-title":"Protocol for micro-purification, enrichment, pre-fractionation and storage of peptides for proteomics using StageTips","volume":"2","author":"Rappsilber","year":"2007","journal-title":"Nat Protoc"},{"key":"B53","doi-asserted-by":"publisher","DOI":"10.1021\/pr101065j","article-title":"Andromeda: A Peptide Search Engine Integrated into the MaxQuant Environment","volume":"10","author":"Cox","year":"2011","journal-title":"J Proteome Res"},{"key":"B54","doi-asserted-by":"publisher","DOI":"10.1038\/nbt.1511","article-title":"MaxQuant enables high peptide identification rates, individualized p.p.b.-range mass accuracies and proteome-wide protein quantification","volume":"26","author":"Cox","year":"2008","journal-title":"Nat Biotechnol"},{"key":"B55","doi-asserted-by":"publisher","DOI":"10.1084\/jem.20131424","article-title":"Consequences of the recurrent MYD88L265P somatic mutation for B cell tolerance","volume":"211","author":"Wang","year":"2014","journal-title":"J Exp Med"},{"key":"B56","doi-asserted-by":"publisher","DOI":"10.1126\/scisignal.aab2820","article-title":"Negative regulation of NF-\u03baB p65 activity by serine 536 phosphorylation","volume":"9","author":"Prad\u00e8re","year":"2016","journal-title":"Sci Signal"},{"key":"B57","doi-asserted-by":"publisher","DOI":"10.1177\/019262339502300503","article-title":"Longevity, Body Weight, and Neoplasia in Ad Libitum-Fed and Diet-Restricted C57BL6 Mice Fed NIH-31 Open Formula Diet","volume":"23","author":"Blackwell","year":"1995","journal-title":"Toxicol Pathol"},{"key":"B58","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2005-09-3613","article-title":"Impaired class switch recombination (CSR) in Waldenstr\u00f6m macroglobulinemia (WM) despite apparently normal CSR machinery","volume":"107","author":"Kriangkum","year":"2006","journal-title":"Blood"},{"key":"B59","doi-asserted-by":"publisher","first-page":"827","DOI":"10.1038\/sj.leu.2404538","article-title":"IgM-expressing Waldenstrom\u2019s macroglobulinemia tumor cells reveal a potential for isotype switch events in vivo","volume":"21","author":"Babbage","year":"2007","journal-title":"Leukemia"},{"key":"B60","doi-asserted-by":"publisher","DOI":"10.1158\/1078-0432.ccr-06-2788","article-title":"Molecular Characterization of Waldenstrom\u2019s Macroglobulinemia Reveals Frequent Occurrence of Two B-Cell Clones Having Distinct IgH VDJ Sequences","volume":"13","author":"Kriangkum","year":"2007","journal-title":"Clin Cancer Res"},{"key":"B61","doi-asserted-by":"publisher","DOI":"10.1111\/j.1365-2141.2006.06397.x","article-title":"Functional class switch recombination may occur \u2018in vivo\u2019 in Waldenstr\u00f6m macroglobulinaemia","volume":"136","author":"Mart\u00edn-Jim\u00e9nez","year":"2007","journal-title":"Brit J Haematol"},{"key":"B62","doi-asserted-by":"crossref","DOI":"10.4049\/jimmunol.140.7.2436","article-title":"Strain-dependent expression of VH gene families","volume":"140","author":"Jeong","year":"1988","journal-title":"J Immunol"},{"key":"B63","doi-asserted-by":"publisher","DOI":"10.1084\/jem.168.1.417","article-title":"Developmentally regulated and strain-specific expression of murine VH gene families","volume":"168","author":"Yancopoulos","year":"1988","journal-title":"J Exp Med"},{"key":"B64","doi-asserted-by":"publisher","DOI":"10.1002\/j.1460-2075.1989.tb08358.x","article-title":"Molecular cloning of the primary IgH repertoire: a quantitative analysis of VH gene usage in adult mice","volume":"8","author":"Sheehan","year":"1989","journal-title":"EMBO J"},{"key":"B65","doi-asserted-by":"publisher","DOI":"10.1016\/s1470-2045(14)70442-5","article-title":"International Myeloma Working Group updated criteria for the diagnosis of multiple myeloma","volume":"15","author":"Rajkumar","year":"2014","journal-title":"Lancet Oncol"},{"key":"B66","doi-asserted-by":"publisher","DOI":"10.1056\/nejmoa01133202","article-title":"Melton LJ. A Long-Term Study of Prognosis in Monoclonal Gammopathy of Undetermined Significance","volume":"346","author":"Kyle","year":"2002","journal-title":"New Engl J Med"},{"key":"B67","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2008-12-194241","article-title":"Monoclonal gammopathy of undetermined significance (MGUS) consistently precedes multiple myeloma: a prospective study","volume":"113","author":"Landgren","year":"2009","journal-title":"Blood"},{"key":"B68","doi-asserted-by":"publisher","DOI":"10.1002\/ajh.21845","article-title":"IgM multiple myeloma: Disease definition, prognosis, and differentiation from Waldenstrom\u2019s macroglobulinemia","volume":"85","author":"Schuster","year":"2010","journal-title":"Am J Hematol"},{"key":"B69","doi-asserted-by":"publisher","DOI":"10.3816\/clml.2011.n.017","article-title":"Differential Diagnosis of IgM MGUS and WM According to B-Lymphoid Infiltration by Morphology and Flow Cytometry","volume":"11","author":"Ocio","year":"2011","journal-title":"Clin Lymphoma Myeloma Leukemia"},{"key":"B70","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2014-09-602565","article-title":"The cellular origin and malignant transformation of Waldenstr\u00f6m macroglobulinemia","volume":"125","author":"Paiva","year":"2015","journal-title":"Blood"},{"key":"B71","doi-asserted-by":"publisher","DOI":"10.1002\/hon.2539","article-title":"Diagnostic framing of IgM monoclonal gammopathy: Focus on Waldenstr\u00f6m macroglobulinemia","volume":"37","author":"Tedeschi","year":"2019","journal-title":"Hematol Oncol"},{"key":"B72","doi-asserted-by":"publisher","DOI":"10.1158\/0008-5472.can-08-3701","article-title":"Identification of Copy Number Abnormalities and Inactivating Mutations in Two Negative Regulators of Nuclear Factor-\u03baB Signaling Pathways in Waldenstr\u00f6m\u2019s Macroglobulinemia","volume":"69","author":"Braggio","year":"2009","journal-title":"Cancer Res"},{"key":"B73","doi-asserted-by":"publisher","first-page":"97","DOI":"10.1038\/s41408-018-0130-3","article-title":"Loss of TNFAIP3 enhances MYD88L265P-driven signaling in non-Hodgkin lymphoma","volume":"8","author":"Wenzl","year":"2018","journal-title":"Blood Cancer J"},{"key":"B74","doi-asserted-by":"publisher","DOI":"10.1016\/j.cancergencyto.2006.04.009","article-title":"6q deletion discriminates Waldenstr\u00f6m macroglobulinemia from IgM monoclonal gammopathy of undetermined significance","volume":"169","author":"Schop","year":"2006","journal-title":"Cancer Genet Cytogen"},{"key":"B75","doi-asserted-by":"publisher","DOI":"10.1111\/j.1365-2141.2006.06389.x","article-title":"6q deletion in Waldenstr\u00f6m macroglobulinemia is associated with features of adverse prognosis","volume":"136","author":"Ocio","year":"2007","journal-title":"Brit J Haematol"},{"key":"B76","doi-asserted-by":"publisher","first-page":"190","DOI":"10.1111\/imr.12792","article-title":"Pathogenic B-cell receptor signaling in lymphoid malignancies: New insights to improve treatment","volume":"291","author":"Young","year":"2019","journal-title":"Immunol Rev"},{"key":"B77","doi-asserted-by":"publisher","DOI":"10.1101\/794024","article-title":"B-cell enforced expression of the mouse ortholog of MYD88L265P is responsible for Waldenstr\u00f6m-like B-cell lymphoma","author":"Ouk","year":"2019","journal-title":"bioRxiv"},{"key":"B78","doi-asserted-by":"publisher","DOI":"10.1158\/0008-5472.can-18-0215","article-title":"MYD88 L265P Mutation in Lymphoid Malignancies","volume":"78","author":"Yu","year":"2018","journal-title":"Cancer Res"},{"key":"B79","doi-asserted-by":"publisher","first-page":"12","DOI":"10.1038\/s41408-020-0277-6","article-title":"SYK is activated by mutated MYD88 and drives pro-survival signaling in MYD88 driven B-cell lymphomas","volume":"10","author":"Munshi","year":"2020","journal-title":"Blood Cancer J"},{"key":"B80","doi-asserted-by":"publisher","DOI":"10.1093\/nar\/gky1106","article-title":"The PRIDE database and related tools and resources in 2019: improving support for quantification data","volume":"47","author":"Perez-Riverol","year":"2018","journal-title":"Nucleic Acids Res"}],"container-title":["Frontiers in Immunology"],"original-title":[],"link":[{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fimmu.2020.602868\/full","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,10,14]],"date-time":"2023-10-14T09:37:00Z","timestamp":1697276220000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fimmu.2020.602868\/full"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2020,12,1]]},"references-count":80,"alternative-id":["10.3389\/fimmu.2020.602868"],"URL":"https:\/\/doi.org\/10.3389\/fimmu.2020.602868","relation":{},"ISSN":["1664-3224"],"issn-type":[{"value":"1664-3224","type":"electronic"}],"subject":[],"published":{"date-parts":[[2020,12,1]]},"article-number":"602868"}}