{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,16]],"date-time":"2026-08-16T14:13:17Z","timestamp":1786889597709,"version":"build-2736575974"},"reference-count":48,"publisher":"Wiley","issue":"1","license":[{"start":{"date-parts":[[2024,1,27]],"date-time":"2024-01-27T00:00:00Z","timestamp":1706313600000},"content-version":"vor","delay-in-days":26,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["HemaSphere"],"published-print":{"date-parts":[[2024,1]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Multiple myeloma (MM) is a heterogeneous malignancy of plasma cells. Despite improvement in the prognosis of MM patients after the introduction of many new drugs in the past decades, MM remains incurable since most patients become treatment\u2010resistant. Cyclin\u2010dependent kinase 6 (CDK6) is activated in many types of cancer and has been associated with drug resistance in MM. However, its association with disease stage, genetic alterations, and outcome\u00a0has not been systematically investigated in large cohorts. Here, we analyzed CDK6 expression using immunohistochemistry in 203 formalin\u2010fixed paraffin\u2010embedded\u00a0samples of 146 patients and four healthy individuals. We found that 61.5% of all MM specimens express CDK6 at various levels. CDK6 expression increased with the progression of disease with a median of 0% of CDK6\u2010positive plasma cells in monoclonal gammopathy of undetermined significance (MGUS) (<jats:italic>n<\/jats:italic>\u2009=\u200910) to 30% in newly diagnosed MM (<jats:italic>n<\/jats:italic>\u2009=\u200978)\u00a0and up to 70% in relapsed cases (<jats:italic>n<\/jats:italic>\u2009=\u200955). The highest median CDK6 was observed in extramedullary myeloma (<jats:italic>n<\/jats:italic>\u2009=\u200912), a highly aggressive manifestation of MM. Longitudinal analyses revealed that CDK6 is significantly increased in lenalidomide\u2010treated patients but not in those who did not receive lenalidomide. Furthermore, we observed that patients who underwent lenalidomide\u2010comprising induction therapy had significantly shorter progression\u2010free survival when their samples were CDK6 positive. These data support that CDK6 protein expression is a marker for aggressive and drug\u2010resistant disease and describes a potential drug target in MM.<\/jats:p>","DOI":"10.1002\/hem3.32","type":"journal-article","created":{"date-parts":[[2024,1,27]],"date-time":"2024-01-27T13:54:10Z","timestamp":1706363650000},"source":"Crossref","is-referenced-by-count":4,"title":["CDK6 protein expression is associated with disease progression and treatment resistance in multiple myeloma"],"prefix":"10.1002","volume":"8","author":[{"given":"Johannes","family":"Steinhart","sequence":"first","affiliation":[{"name":"Department of Pathology Ulm University Hospital Ulm Germany"},{"name":"Department of Internal Medicine III Ulm University Hospital Ulm Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Peter","family":"M\u00f6ller","sequence":"additional","affiliation":[{"name":"Department of Pathology Ulm University Hospital Ulm Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Miriam","family":"Kull","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine III Ulm University Hospital Ulm Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jan","family":"Kr\u00f6nke","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine III Ulm University Hospital Ulm Germany"},{"name":"Department of Hematology, Oncology and Cancer Immunology, Charit\u00e9 \u2010 Universit\u00e4tsmedizin Berlin corporate member of Freie Universit\u00e4t Berlin and Humboldt\u2010Universit\u00e4t zu Berlin Berlin Germany"},{"name":"German Cancer Consortium (DKTK) partner site Berlin and German Cancer Research Center (DKFZ) Heidelberg Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Thomas F. 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