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The symptoms of patients with WM can be attributed to the extent and tissue sites of tumor cell infiltration and the magnitude and immunological specificity of the paraprotein. WM presents fascinating clues on neoplastic B-cell development, including the recent discovery of a specific gain-of-function mutation in the MYD88 adapter protein. This not only provides an intriguing link to new findings that natural effector IgM\n                    <jats:sup>+<\/jats:sup>\n                    IgD\n                    <jats:sup>+<\/jats:sup>\n                    memory B-cells are dependent on MYD88 signaling, but also supports the hypothesis that WM derives from primitive, innate-like B-cells, such as marginal zone and B1 B-cells. Following a brief review of the clinical aspects and natural history of WM, this review discusses the thorny issue of WM\u2019s cell of origin in greater depth. Also included are emerging, genetically engineered mouse models of human WM that may enhance our understanding of the biologic and genetic underpinnings of the disease and facilitate the design and testing of new approaches to treat and prevent WM more effectively.\n                  <\/jats:p>","DOI":"10.1155\/2013\/815325","type":"journal-article","created":{"date-parts":[[2013,9,9]],"date-time":"2013-09-09T17:44:45Z","timestamp":1378748685000},"page":"1-25","source":"Crossref","is-referenced-by-count":19,"title":["Waldenstr\u00f6m Macroglobulinemia: Clinical and Immunological Aspects, Natural History, Cell of Origin, and Emerging Mouse Models"],"prefix":"10.1155","volume":"2013","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-2229-5511","authenticated-orcid":true,"given":"Siegfried","family":"Janz","sequence":"first","affiliation":[{"name":"Department of Pathology, University of Iowa Carver College of Medicine, 1030 ML, Iowa City, IA 52242, 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