{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,11,2]],"date-time":"2025-11-02T07:25:41Z","timestamp":1762068341448,"version":"build-2065373602"},"reference-count":53,"publisher":"MDPI AG","issue":"19","license":[{"start":{"date-parts":[[2022,10,7]],"date-time":"2022-10-07T00:00:00Z","timestamp":1665100800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Else Kr\u00f6ner-Fresenius-Stiftung","award":["2010_Kolleg24","SFB1074 Project B2"],"award-info":[{"award-number":["2010_Kolleg24","SFB1074 Project B2"]}]},{"name":"German Research Foundation DFG","award":["2010_Kolleg24","SFB1074 Project B2"],"award-info":[{"award-number":["2010_Kolleg24","SFB1074 Project B2"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Cancers"],"abstract":"<jats:p>Background: CD20 expression is a controversial issue regarding response prediction to anti-CD20 therapy in chronic lymphocytic leukemia (CLL). Methods: Median fluorescence intensities (MFIs) of standard fluorescence beads from the daily calibration of flow cytometers according to EuroFlow protocols were used to establish a normalization approach to study CD20 expression on CLL cells. CD20 MFI was retrospectively assessed prior to and during treatment from flow cytometric measurements of peripheral blood in patients with different depths of molecular response in the four phase-II CLL2-BXX trials (BIG; BAG; BIO; BCG; N = 194) administering either Obinutuzumab or Ofatumumab in combination with targeted agents. Results: No significant difference was observed between the normalized and measured MFIs of CD19 and CD20 on CLL cells. During treatment, CD20 expression levels on CLL cells did not significantly differ between the four investigated different treatment schemes, but a strong molecular response to Ofatumumab seemed to correlate with higher CD20 expression prior to therapy. Conclusions: Standardized staining and instrument monitoring enable a robust assessment of longitudinal biological variations of marker expression based on MFI values. Obinutuzumab showed a higher proportion of patients with a strong MRD response independent from initial CD20 expression, whereas high pre-therapeutic CD20 expression levels seem to correlate with a profound response to Ofatumumab.<\/jats:p>","DOI":"10.3390\/cancers14194917","type":"journal-article","created":{"date-parts":[[2022,10,8]],"date-time":"2022-10-08T01:52:21Z","timestamp":1665193941000},"page":"4917","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":6,"title":["CD20 Expression as a Possible Novel Prognostic Marker in CLL: Application of EuroFlow Standardization Technique and Normalization Procedures in Flow Cytometric Expression Analysis"],"prefix":"10.3390","volume":"14","author":[{"given":"Anke","family":"Schilhabel","sequence":"first","affiliation":[{"name":"Laboratory for Specialized Hematological Diagnostics, Medical Department II, University Hospital Schleswig-Holstein, 24105 Kiel, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Peter Jonas","family":"Walter","sequence":"additional","affiliation":[{"name":"Laboratory for Specialized Hematological Diagnostics, Medical Department II, University Hospital Schleswig-Holstein, 24105 Kiel, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Paula","family":"Cramer","sequence":"additional","affiliation":[{"name":"Department I of Internal Medicine, Center for Integrated Oncology Aachen Bonn Cologne Duesseldorf, German CLL Study Group, University Hospital Cologne, 50924 Cologne, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Julia","family":"von Tresckow","sequence":"additional","affiliation":[{"name":"Department of Hematology and Stem Cell Transplantation, West German Cancer Center, University Hospital Essen, University of Duisburg-Essen, 45147 Essen, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Saskia","family":"Kohlscheen","sequence":"additional","affiliation":[{"name":"Laboratory for Specialized Hematological Diagnostics, Medical Department II, University Hospital Schleswig-Holstein, 24105 Kiel, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5482-8880","authenticated-orcid":false,"given":"Monika","family":"Szczepanowski","sequence":"additional","affiliation":[{"name":"Laboratory for Specialized Hematological Diagnostics, Medical Department II, University Hospital Schleswig-Holstein, 24105 Kiel, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Anna","family":"Laqua","sequence":"additional","affiliation":[{"name":"Laboratory for Specialized Hematological Diagnostics, Medical Department II, University Hospital Schleswig-Holstein, 24105 Kiel, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Kirsten","family":"Fischer","sequence":"additional","affiliation":[{"name":"Department I of Internal Medicine, Center for Integrated Oncology Aachen Bonn Cologne Duesseldorf, German CLL Study Group, University Hospital Cologne, 50924 Cologne, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Barbara","family":"Eichhorst","sequence":"additional","affiliation":[{"name":"Department I of Internal Medicine, Center for Integrated Oncology Aachen Bonn Cologne Duesseldorf, German CLL Study Group, University Hospital Cologne, 50924 Cologne, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3603-761X","authenticated-orcid":false,"given":"Sebastian","family":"B\u00f6ttcher","sequence":"additional","affiliation":[{"name":"Hematology, Oncology, Palliative Care, Clinic for Internal Medicine III, Rostock University Medical School, 18057 Rostock, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Christof","family":"Schneider","sequence":"additional","affiliation":[{"name":"Department III of Internal Medicine, Ulm University, 89081 Ulm, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Eugen","family":"Tausch","sequence":"additional","affiliation":[{"name":"Department III of Internal Medicine, Ulm University, 89081 Ulm, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Monika","family":"Br\u00fcggemann","sequence":"additional","affiliation":[{"name":"Laboratory for Specialized Hematological Diagnostics, Medical Department II, University Hospital Schleswig-Holstein, 24105 Kiel, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Michael","family":"Kneba","sequence":"additional","affiliation":[{"name":"Laboratory for Specialized Hematological Diagnostics, Medical Department II, University Hospital Schleswig-Holstein, 24105 Kiel, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Michael","family":"Hallek","sequence":"additional","affiliation":[{"name":"Department I of Internal Medicine, Center for Integrated Oncology Aachen Bonn Cologne Duesseldorf, German CLL Study Group, University Hospital Cologne, 50924 Cologne, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Matthias","family":"Ritgen","sequence":"additional","affiliation":[{"name":"Laboratory for Specialized Hematological Diagnostics, Medical Department II, University Hospital Schleswig-Holstein, 24105 Kiel, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2022,10,7]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"1494","DOI":"10.3324\/haematol.2019.243543","article-title":"The regulation and function of CD20: An \u201cenigma\u201d of B-cell biology and targeted 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