{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,29]],"date-time":"2026-05-29T09:03:41Z","timestamp":1780045421554,"version":"3.53.1"},"reference-count":62,"publisher":"Wiley","issue":"5","license":[{"start":{"date-parts":[[2026,4,29]],"date-time":"2026-04-29T00:00:00Z","timestamp":1777420800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2026,4,29]],"date-time":"2026-04-29T00:00:00Z","timestamp":1777420800000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"funder":[{"DOI":"10.13039\/501100001659","name":"Deutsche Forschungsgemeinschaft","doi-asserted-by":"publisher","award":["SFB1074 B10N"],"award-info":[{"award-number":["SFB1074 B10N"]}],"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":[[2026,5]]},"abstract":"Abstract<\/jats:title>\n \n Approximately 1% of chronic lymphocytic leukemia (CLL) cases harbor a translocation juxtaposing the\n immunoglobulin heavy chain<\/jats:italic>\n (\n IGH<\/jats:italic>\n ) and\n B\u2010cell lymphoma 3<\/jats:italic>\n (\n BCL3<\/jats:italic>\n ) loci. Aiming at comprehensive molecular characterization of\n IGH<\/jats:italic>\n ::\n BCL3\u2010<\/jats:italic>\n positive B\u2010cell neoplasms, we here investigated samples from 84 patients using fluorescence in situ hybridization (FISH), whole\u2010genome and targeted sequencing, and DNA methylation analyses. Junctional sequences obtained in 27 patients showed breakpoints upstream of\n BCL3<\/jats:italic>\n in all CLL cases.\n IGH<\/jats:italic>\n breaks were presumably driven by aberrant class\u2010switch recombination in 26\/27 cases, frequently involving\n IGHA<\/jats:italic>\n (12\/26). Notably, 95% (78\/82) of patients carried an unmutated\n IGHV<\/jats:italic>\n with significant CLL stereotype subset #8 enrichment. Trisomy 12 (61%, 51\/83) and mutations affecting\n NOTCH1<\/jats:italic>\n (32%, 25\/79),\n BRAF<\/jats:italic>\n (14%, 11\/79), and\n FBXW7<\/jats:italic>\n (14%, 11\/79) were frequent aberrations. DNA methylation analysis assigned 77% (51\/66) of patients with\n IGH<\/jats:italic>\n ::\n BCL3\u2010<\/jats:italic>\n translocation with at least 60% tumor cell content to the naive B\u2010cell\u2010like group but unraveled a distinct and during follow\u2010up stable signature resembling in part plasma cell\u2010like epigenetic features. A binary DNA methylation classifier using 20 CpGs could distinguish\n IGH<\/jats:italic>\n ::\n BCL3<\/jats:italic>\n \u2010translocated CLL samples from other CLL subtypes. In an efficacy cohort of 3832 previously untreated patients from GCLLSG trials,\n IGH::BCL3<\/jats:italic>\n was associated with shorter progression\u2010free survival (PFS) and overall survival (OS) in 28 patients when treated with chemoimmunotherapy, but not in those receiving venetoclax. Our findings highlight the genetic and epigenetic homogeneity of\n IGH<\/jats:italic>\n ::\n BCL3<\/jats:italic>\n \u2010translocated CLL samples and their differences from other types of CLL, suggesting\n IGH<\/jats:italic>\n ::\n BCL3<\/jats:italic>\n leukemic B\u2010cell neoplasms to be a biological distinct type within the spectrum of mature lymphatic leukemia\/CLL.\n <\/jats:p>","DOI":"10.1002\/hem3.70354","type":"journal-article","created":{"date-parts":[[2026,4,29]],"date-time":"2026-04-29T10:05:41Z","timestamp":1777457141000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Chronic lymphocytic leukemia with\n IGH<\/i>\n ::\n BCL3<\/i>\n \u2010translocation is characterized by a homogeneous and distinct genetic and epigenetic landscape"],"prefix":"10.1002","volume":"10","author":[{"ORCID":"https:\/\/orcid.org\/0009-0008-5160-4732","authenticated-orcid":false,"given":"Cosima","family":"Drewes","sequence":"first","affiliation":[{"name":"Institute of Human Genetics, Ulm University and Ulm University Medical Center Ulm Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Cristina","family":"L\u00f3pez","sequence":"additional","affiliation":[{"name":"Institute of Human Genetics, Ulm University and Ulm University Medical Center Ulm Germany"},{"name":"Molecular Pathology of Lymphoid Neoplasms Group Institut d'Investigaciones Biom\u00e8diques August Pi i Sunyer (IDIBAPS) Barcelona Spain"},{"name":"Hematopathology Section, Pathology Department Hospital Cl\u00ednic de Barcelona Barcelona Spain"},{"name":"Departament de Fonaments Cl\u00ednics Universitat de Barcelona Barcelona Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0005-6120-9195","authenticated-orcid":false,"given":"Juan Emilio","family":"Martinez\u2010Manj\u00f3n","sequence":"additional","affiliation":[{"name":"Department of Computer Science and Artificial Intelligence University of Granada, Andalusian Research Institute in Data Science and Computational Intelligence Granada Spain"},{"name":"Instituto de Investigaci\u00f3n Sanitaria ibs, GRANADA, Hospitales Universitarios de Granada\u2010Universidad de Granada Granada Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nnamdi","family":"Okeke","sequence":"additional","affiliation":[{"name":"Institute of Human Genetics, Ulm University and Ulm University Medical Center Ulm Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Billy","family":"Jebaraj","sequence":"additional","affiliation":[{"name":"Division of CLL, Department of Internal Medicine III Ulm University Medical Center Ulm Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Susanne","family":"Bens","sequence":"additional","affiliation":[{"name":"Institute of Human Genetics, Ulm University and Ulm University Medical Center Ulm Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bj\u00f6rn","family":"Br\u00e4ndl","sequence":"additional","affiliation":[{"name":"Department of Psychiatry and Psychotherapy Zentrum f\u00fcr Integrative Psychiatrie gGmbH, Universit\u00e4tsklinikum Schleswig\u2010Holstein, Campus Kiel Kiel Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Martin J. S.","family":"Dyer","sequence":"additional","affiliation":[{"name":"The Ernest and Helen Scott Haematological Research Institute, Leicester Cancer Research Centre University of Leicester Leicester UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9990-6918","authenticated-orcid":false,"given":"Barbara","family":"Eichhorst","sequence":"additional","affiliation":[{"name":"Department I of Internal Medicine and German CLL Study Group Center for Integrated Oncology Aachen Bonn Cologne Duesseldorf (CIO ABCD), University of Cologne, Faculty of Medicine and University Hospital of Cologne Cologne Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anja","family":"Fischer","sequence":"additional","affiliation":[{"name":"Institute of Human Genetics, Ulm University and Ulm University Medical Center Ulm Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kirsten","family":"Fischer","sequence":"additional","affiliation":[{"name":"Department I of Internal Medicine and German CLL Study Group Center for Integrated Oncology Aachen Bonn Cologne Duesseldorf (CIO ABCD), University of Cologne, Faculty of Medicine and University Hospital of Cologne Cologne Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sandra","family":"Robrecht","sequence":"additional","affiliation":[{"name":"Department I of Internal Medicine and German CLL Study Group Center for Integrated Oncology Aachen Bonn Cologne Duesseldorf (CIO ABCD), University of Cologne, Faculty of Medicine and University Hospital of Cologne Cologne Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michael","family":"Hallek","sequence":"additional","affiliation":[{"name":"Department I of Internal Medicine and German CLL Study Group Center for Integrated Oncology Aachen Bonn Cologne Duesseldorf (CIO ABCD), University of Cologne, Faculty of Medicine and University Hospital of Cologne Cologne Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Selina","family":"Glaser","sequence":"additional","affiliation":[{"name":"Institute of Human Genetics, Ulm University and Ulm University Medical Center Ulm Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sina","family":"Hillebrecht","sequence":"additional","affiliation":[{"name":"Institute of Human Genetics, Ulm University and Ulm University Medical Center Ulm Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sandrine","family":"Jayne","sequence":"additional","affiliation":[{"name":"The Ernest and Helen Scott Haematological Research Institute, Leicester Cancer Research Centre University of Leicester Leicester UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Helene","family":"Kretzmer","sequence":"additional","affiliation":[{"name":"Department of Genome Regulation Max Planck Institute for Molecular Genetics Berlin Germany"},{"name":"Digital Health Cluster, Hasso Plattner Institute for Digital Engineering, Digital Engineering Faculty University of Potsdam Potsdam Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anja","family":"Mottok","sequence":"additional","affiliation":[{"name":"Institute of Human Genetics, Ulm University and Ulm University Medical Center Ulm Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Franz\u2010Josef","family":"M\u00fcller","sequence":"additional","affiliation":[{"name":"Department of Psychiatry and Psychotherapy Zentrum f\u00fcr Integrative Psychiatrie gGmbH, Universit\u00e4tsklinikum Schleswig\u2010Holstein, Campus Kiel Kiel 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Granada\u2010Universidad de Granada Granada Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stephan","family":"Stilgenbauer","sequence":"additional","affiliation":[{"name":"Division of CLL, Department of Internal Medicine III Ulm University Medical Center Ulm Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Eugen","family":"Tausch","sequence":"additional","affiliation":[{"name":"Division of CLL, Department of Internal Medicine III Ulm University Medical Center Ulm Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Reiner","family":"Siebert","sequence":"additional","affiliation":[{"name":"Institute of Human Genetics, Ulm University and Ulm University Medical Center Ulm Germany"},{"name":"German Center for Child and Adolescent Health (DZKJ), Partner Site Ulm Ulm 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