{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,26]],"date-time":"2026-08-26T01:40:06Z","timestamp":1787708406478,"version":"build-2784847793"},"reference-count":35,"publisher":"Wiley","issue":"1","license":[{"start":{"date-parts":[[2025,1,23]],"date-time":"2025-01-23T00:00:00Z","timestamp":1737590400000},"content-version":"vor","delay-in-days":22,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001659","name":"Deutsche Forschungsgemeinschaft","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100001659","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["HemaSphere"],"published-print":{"date-parts":[[2025,1]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>The definition of high\u2010risk (HR) multiple myeloma (MM) is still a matter of debate. We prospectively evaluated the HR detection using FISH in combination with SKY92 gene expression profiling in 258 MM patients (newly diagnosed [ND] MM: <jats:italic>n<\/jats:italic>\u2009=\u2009109; relapsed\/refractory [RR] MM: <jats:italic>n<\/jats:italic>\u2009=\u2009149). HR SKY92 was significantly enriched in RRMM (57\/121, 47.1%) compared with NDMM (17\/95, 17.9%) (<jats:italic>p<\/jats:italic>\u2009&lt;\u20090.0001). RRMM patients with HR SKY92 showed significantly shorter progression\u2010free survival (PFS) (<jats:italic>p<\/jats:italic>\u2009&lt;\u20090.0001) and overall survival (OS) (<jats:italic>p<\/jats:italic>\u2009&lt;\u20090.0001) than SKY92 standard\u2010risk (SR). In NDMM, HR SKY92 also indicated a significantly inferior PFS (<jats:italic>p<\/jats:italic>\u2009&lt;\u20090.0001) in comparison with SR. We combined SKY92 with FISH (HR: t(4;14), del17p, +1q21 according to R2\u2010ISS) in 181 patients (NDMM: <jats:italic>n<\/jats:italic>\u2009=\u200979; RRMM: <jats:italic>n<\/jats:italic>\u2009=\u2009102). We found a discrepancy between both risk stratification systems, with only 49 (27.1%) patients being defined as HR by both SKY92 and FISH (\u201cdouble HR\u201d). In terms of survival outcomes, \u201cdouble HR\u201d presented a negative prognostic factor for PFS in both NDMM (<jats:italic>p<\/jats:italic>\u2009&lt;\u20090.0001) and RRMM (<jats:italic>p<\/jats:italic>\u2009&lt;\u20090.0001). Furthermore, \u201cdouble\u2010HR\u201d patients showed the worst OS (<jats:italic>p<\/jats:italic>\u2009=\u20090.000\u200913) in RRMM. Additionally, whole genome sequencing (WGS) revealed <jats:italic>CRBN<\/jats:italic> mutation (<jats:italic>n<\/jats:italic>\u2009=\u20093) and bi\u2010allelic events (mutation and\/or deletion) in <jats:italic>TP53<\/jats:italic> (<jats:italic>n<\/jats:italic>\u2009=\u20097) and <jats:italic>TNFRSF17<\/jats:italic> (<jats:italic>n<\/jats:italic>\u2009=\u20091). Altogether, we provide the first prospective real\u2010world evidence that the combination SKY92 and FISH (according to R2\u2010ISS) identifies a subset of patients with ultra\u2010HR MM, and WGS complements SKY92 and FISH in MM risk stratification.<\/jats:p>","DOI":"10.1002\/hem3.70078","type":"journal-article","created":{"date-parts":[[2025,1,23]],"date-time":"2025-01-23T08:01:05Z","timestamp":1737619265000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":4,"title":["Combining SKY92 gene expression profiling and FISH (according to R2\u2010ISS) defines ultra\u2010high\u2010risk Multiple Myeloma"],"prefix":"10.1002","volume":"9","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-5772-7700","authenticated-orcid":false,"given":"Xiang","family":"Zhou","sequence":"first","affiliation":[{"name":"Department of Internal Medicine II University Hospital of W\u00fcrzburg W\u00fcrzburg Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Annika","family":"Hofmann","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine II University Hospital of W\u00fcrzburg W\u00fcrzburg Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Benedict","family":"Engel","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine II University Hospital of W\u00fcrzburg W\u00fcrzburg Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Cornelia","family":"Vogt","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine II University Hospital of W\u00fcrzburg W\u00fcrzburg Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Silvia","family":"Nerreter","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine II University Hospital of W\u00fcrzburg W\u00fcrzburg Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yoko","family":"Tamamushi","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine II University Hospital of W\u00fcrzburg W\u00fcrzburg Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Friederike","family":"Schmitt","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine II University Hospital of W\u00fcrzburg W\u00fcrzburg Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maria","family":"leberzammer","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine II University Hospital of W\u00fcrzburg W\u00fcrzburg Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Emilia","family":"Stanojkovska","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine II University Hospital of W\u00fcrzburg W\u00fcrzburg Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marietta","family":"Truger","sequence":"additional","affiliation":[{"name":"Munich Leukemia Laboratory (MLL) Munich Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xianghui","family":"Xiao","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine II University Hospital of W\u00fcrzburg W\u00fcrzburg Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christine","family":"Riedhammer","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine II University Hospital of W\u00fcrzburg W\u00fcrzburg Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maximilian J.","family":"Steinhardt","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine II University Hospital of W\u00fcrzburg W\u00fcrzburg Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mara","family":"John","sequence":"additional","affiliation":[{"name":"Mildred Scheel Early Career Center W\u00fcrzburg Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Julia","family":"Mersi","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine II University Hospital of W\u00fcrzburg W\u00fcrzburg Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Seungbin","family":"Han","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine II University Hospital of W\u00fcrzburg W\u00fcrzburg Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Umair","family":"Munawar","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine II University Hospital of W\u00fcrzburg W\u00fcrzburg Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Johannes 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