Immunogenomic characterization of classic Hodgkin lymphoma variant of Richter transformation reveals shared biology with de novo classic Hodgkin lymphoma
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). Previous studies suggest that type 1 represents an earlier stage of type 2 and that both may be clonally related to the underlying CLL/SLL. However, the immune evasion phenotype of HRS cells in CHL-RT and the genetic features of precursor CLL/SLL remain incompletely defined. In this multi-institutional study of 77 patients with CHL-RT (27 type 1 and 50 type 2), we characterized immune evasion markers, PD-L1/PD-L2 copy number alterations, tumor microenvironment, and performed targeted next-generation sequencing on 37 CLL/SLL samples. HRS cells in both CHL-RT subtypes showed immune evasion features largely resembling de novo CHL. However, PD-L1 expression was less frequent in type 1 than type 2 CHL-RT (53.3% vs. 100%, p.
Authors
- Neil E. Kay (ORCID: https://orcid.org/0000-0002-5951-5055)
- Sameer Ashok Parikh (ORCID: https://orcid.org/0000-0002-3221-7314)
- Rebecca L. King (ORCID: https://orcid.org/0000-0002-7132-0226)
- Katherine C. Lopez (ORCID: https://orcid.org/0000-0002-7549-8849)
- Özgür Can Eren (ORCID: https://orcid.org/0000-0001-9889-2702)
- Ahmet Doǧan (ORCID: https://orcid.org/0000-0001-6576-5256)
- Mingfei Yan (ORCID: https://orcid.org/0000-0002-2054-5986)
- Paul Joseph Hampel (ORCID: https://orcid.org/0000-0003-1292-3024)
- Megan S. Lim (ORCID: https://orcid.org/0000-0002-0415-2867)
- Leonardo Boiocchi (ORCID: https://orcid.org/0000-0001-5188-6217)
- Wenbin Xiao (ORCID: https://orcid.org/0000-0001-8586-8500)
- Nathaniel Aleynick (ORCID: https://orcid.org/0000-0002-3726-1285)
- Alexander C. L. Chan (ORCID: https://orcid.org/0000-0001-5884-8424)
- Kari G. Rabe (ORCID: https://orcid.org/0000-0002-7313-1875)
- Mikhail Roshal (ORCID: https://orcid.org/0000-0002-9585-0790)
- Michelly Sampaio De Melo (ORCID: https://orcid.org/0000-0002-5447-7440)
- Sutapa Sinha (ORCID: https://orcid.org/0000-0002-7274-9622)
- Elaine S. Jaffe (ORCID: https://orcid.org/0000-0003-4632-0301)
- Alexa Cohen
- Yanming Zhang
Institutions
- Mayo Clinic (US)
- Memorial Sloan Kettering Cancer Center (US)
- National Cancer Institute (US)
- Center for Cancer Research (US)
Publication Details
- Journal
- Haematologica
- Published
- 2026-10-29
- DOI
- https://doi.org/10.3324/haematol.2026.301780
- Primary Topic
- Chronic Lymphocytic Leukemia Research
- Type
- article
- Field-Weighted Citation Impact
- 0.00