{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"institution":[{"name":"medRxiv"}],"indexed":{"date-parts":[[2026,5,23]],"date-time":"2026-05-23T02:05:54Z","timestamp":1779501954059,"version":"3.53.1"},"posted":{"date-parts":[[2026,5,20]]},"group-title":"Hematology","reference-count":30,"publisher":"openRxiv","license":[{"start":{"date-parts":[[2026,5,20]],"date-time":"2026-05-20T00:00:00Z","timestamp":1779235200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"accepted":{"date-parts":[[2026,5,20]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                <jats:p>\n                  Richter transformation of Chronic lymphocytic leukemia\/small lymphocytic lymphoma (CLL\/SLL) into classic Hodgkin lymphoma (CHL-RT) is rare and remains incompletely understood. Two histologic subtypes are recognized: type 1 (CLL\/SLL with scattered Hodgkin\/Reed-Sternberg (HRS) cells) and type 2 (HRS cells within a polymorphous inflammatory background). In this multi-institutional study of 77 patients with CHL-RT (27 type 1 and 50 type 2), we characterized immune evasion markers,\n                  <jats:italic>PD-L1<\/jats:italic>\n                  \/\n                  <jats:italic>PD-L2<\/jats:italic>\n                  copy number alterations, tumor microenvironment, and performed targeted next-generation sequencing on 37 CLL\/SLL samples. HRS cells in CHL-RT displayed immune-evasion phenotypes similar to de novo CHL, though PD-L1 expression was lower in type 1 cases.\n                  <jats:italic>PD-L1\/PD-L2<\/jats:italic>\n                  gain\/polysomy were frequent (83.3%). CLL\/SLL with CHL-RT harbored increased mutations in\n                  <jats:italic>XPO1, FBXW7, BIRC3, TRAF3<\/jats:italic>\n                  , and\n                  <jats:italic>HLA-A<\/jats:italic>\n                  versus reference CLL\/SLL. Similar mutational profiles, demographics, and survival outcomes support a biological continuum between type 1 and type 2 CHL-RT, with distinct genetic features in CLL\/SLL predisposing to CHL transformation.\n                <\/jats:p>\n                <jats:sec>\n                  <jats:title>STATEMENT OF SIGNIFICANCE<\/jats:title>\n                  <jats:p>Classic Hodgkin lymphoma-type Richter transformation arises from convergent Hodgkin-like immune evasion on a genetically primed CLL\/SLL background. Through integrated genomic and tumor microenvironment analyses in a large multicenter cohort, we establish this as a biologically coherent entity and provide rationale for PD-L1\/PD-L2-directed therapeutic strategies.<\/jats:p>\n                <\/jats:sec>","DOI":"10.64898\/2026.05.11.26352584","type":"posted-content","created":{"date-parts":[[2026,5,21]],"date-time":"2026-05-21T01:45:21Z","timestamp":1779327921000},"source":"Crossref","is-referenced-by-count":0,"title":["Genetic risk and immune dysregulation of classic Hodgkin lymphoma transformation of chronic lymphocytic leukemia\/small lymphocytic lymphoma: a multicentric study"],"prefix":"10.64898","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-2054-5986","authenticated-orcid":false,"given":"Mingfei","family":"Yan","sequence":"first","affiliation":[{"name":"Department of Pathology and Laboratory Medicine, Memorial Sloan Kettering Cancer Center, New York, NY"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3221-7314","authenticated-orcid":false,"given":"Sameer A.","family":"Parikh","sequence":"additional","affiliation":[{"name":"Division of Hematology, Department of Medicine, Mayo Clinic, Rochester, MN"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5447-7440","authenticated-orcid":false,"given":"Michelly K.","family":"Sampaio De Melo","sequence":"additional","affiliation":[{"name":"Laboratory of Pathology, Center for Cancer Research, National Cancer Institute, Bethesda, MD"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1292-3024","authenticated-orcid":false,"given":"Paul J.","family":"Hampel","sequence":"additional","affiliation":[{"name":"Division of Hematology, Department of Medicine, Mayo Clinic, Rochester, MN"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3726-1285","authenticated-orcid":false,"given":"Nathaniel","family":"Aleynick","sequence":"additional","affiliation":[{"name":"Department of Pathology and Laboratory Medicine, Memorial Sloan Kettering Cancer Center, New York, NY"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5884-8424","authenticated-orcid":false,"given":"Alexander","family":"Chan","sequence":"additional","affiliation":[{"name":"Department of Pathology and Laboratory Medicine, Memorial Sloan Kettering Cancer Center, New York, NY"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9889-2702","authenticated-orcid":false,"given":"Ozgur Can","family":"Eren","sequence":"additional","affiliation":[{"name":"Department of Pathology and Laboratory Medicine, Memorial Sloan Kettering Cancer Center, New York, NY"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Katherine","family":"Lopez","sequence":"additional","affiliation":[{"name":"Department of Pathology and Laboratory Medicine, Memorial Sloan Kettering Cancer Center, New York, NY"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alexa","family":"Cohen","sequence":"additional","affiliation":[{"name":"Department of Pathology and Laboratory Medicine, Memorial Sloan Kettering Cancer Center, New York, NY"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mikhail","family":"Roshal","sequence":"additional","affiliation":[{"name":"Department of Pathology and Laboratory Medicine, Memorial Sloan Kettering Cancer Center, New York, NY"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0415-2867","authenticated-orcid":false,"given":"Megan S.","family":"Lim","sequence":"additional","affiliation":[{"name":"Department of Pathology and Laboratory Medicine, Memorial Sloan Kettering Cancer Center, New York, NY"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5188-6217","authenticated-orcid":false,"given":"Leonardo","family":"Boiocchi","sequence":"additional","affiliation":[{"name":"Department of Pathology and Laboratory Medicine, Memorial Sloan Kettering Cancer Center, New York, NY"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6576-5256","authenticated-orcid":false,"given":"Ahmet","family":"Dogan","sequence":"additional","affiliation":[{"name":"Department of Pathology and Laboratory Medicine, Memorial Sloan Kettering Cancer Center, New York, NY"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yanming","family":"Zhang","sequence":"additional","affiliation":[{"name":"Department of Pathology and Laboratory Medicine, Memorial Sloan Kettering Cancer Center, New York, 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