{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,5]],"date-time":"2026-05-05T17:09:18Z","timestamp":1778000958714,"version":"3.51.4"},"reference-count":47,"publisher":"American Society of Hematology","issue":"1","content-domain":{"domain":["ashpublications.org"],"crossmark-restriction":true},"short-container-title":[],"published-print":{"date-parts":[[2021,12,10]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>In the 1960s, Dr Jan Waldenstr\u00f6m argued that patients who had monoclonal proteins without any symptoms or evidence of end-organ damage represented a benign monoclonal gammopathy. In 1978, Dr Robert Kyle introduced the concept of \u201cmonoclonal gammopathy of undetermined significance\u201d (MGUS) given that, at diagnosis, it was not possible with available methods (ie, serum protein electrophoresis to define the concentration of M-proteins and microscopy to determine the plasma cell percentage in bone marrow aspirates) to determine which patients would ultimately progress to multiple myeloma. The application of low-input whole-genome sequencing (WGS) technology has circumvented previous problems related to volume of clonal plasma cells and contamination by normal plasma cells and allowed for the interrogation of the WGS landscape of MGUS. As discussed in this chapter, the distribution of genetic events reveals striking differences and the existence of 2 biologically and clinically distinct entities of asymptomatic monoclonal gammopathies. Thus, we already have genomic tools to identify \u201cmyeloma-defining genomic events,\u201d and consequently, it is reasonable to consider updating our preferred terminologies. When the clinical field is ready to move forward, we should be able to consolidate current terminologies\u2014from current 7 clinical categories: low-risk MGUS, intermediate-risk MGUS, high-risk MGUS, low-risk smoldering myeloma, intermediate-risk smoldering myeloma, high-risk smoldering myeloma, and multiple myeloma\u2014to future 3 genomic-based categories: monoclonal gammopathy, early detection of multiple myeloma (in which myeloma-defining genomic events already have been acquired), and multiple myeloma (patients who are already progressing and clinically defined cases). Ongoing investigations will continue to advance the field.<\/jats:p>","DOI":"10.1182\/hematology.2021000303","type":"journal-article","created":{"date-parts":[[2021,12,10]],"date-time":"2021-12-10T07:20:54Z","timestamp":1639120854000},"page":"662-672","update-policy":"https:\/\/doi.org\/10.1182\/blood.2019cm0000","source":"Crossref","is-referenced-by-count":20,"title":["Advances in MGUS diagnosis, risk stratification, and management: introducing myeloma-defining genomic events"],"prefix":"10.1182","volume":"2021","author":[{"given":"Ola","family":"Landgren","sequence":"first","affiliation":[{"name":"Myeloma Program, Sylvester Comprehensive Cancer Center, University of Miami, Miami, FL"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"234","published-online":{"date-parts":[[2021,12,10]]},"reference":[{"issue":"6","key":"2021121012091219200_hem2021000303C1","doi-asserted-by":"crossref","first-page":"1121","DOI":"10.1038\/leu.2010.60","article-title":"Monoclonal gammopathy of undetermined significance (MGUS) and smoldering (asymptomatic) multiple myeloma: IMWG consensus perspectives risk factors for progression and guidelines for monitoring and management","volume":"24","author":"Kyle","year":"2010","journal-title":"Leukemia"},{"issue":"22","key":"2021121012091219200_hem2021000303C2","doi-asserted-by":"crossref","first-page":"5412","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"},{"issue":"3-4","key":"2021121012091219200_hem2021000303C3","doi-asserted-by":"crossref","first-page":"216","DOI":"10.1111\/j.0954-6820.1944.tb03955.x","article-title":"Incipient myelomatosis or \u2018essential\u2019 hyperglobulinemia with fibrinogenopenia\u2014a new syndrome","volume":"117","author":"Waldenstr\u00f6m","year":"1944","journal-title":"Acta Med Scand"},{"issue":"1","key":"2021121012091219200_hem2021000303C4","doi-asserted-by":"crossref","first-page":"24","DOI":"10.1016\/0002-9343(57)90335-2","article-title":"Glycoproteins in serum from patients with myeloma, macroglobulinemia and related conditions","volume":"22","author":"Laurell","year":"1957","journal-title":"Am J Med"},{"key":"2021121012091219200_hem2021000303C5","first-page":"1","article-title":"Studies on \u201cabnormal\u201d serum globulins (M-components) in myeloma, macroglobulinemia and related diseases","volume":"367","author":"Heremans","year":"1961","journal-title":"Acta Med Scand Suppl"},{"issue":"5","key":"2021121012091219200_hem2021000303C6","doi-asserted-by":"crossref","first-page":"814","DOI":"10.1016\/0002-9343(78)90522-3","article-title":"Monoclonal gammopathy of undetermined significance. 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