Tsagiopoulou, MariaChapaprieta, VicenteRussiñol, NuriaGarcía Torre, BeatrizPechlivanis, NikolaosNadeu Prat, FerranPapakonstantinou, NikosStavroyianni, NikiChatzidimitriou, AnastasiaPsomopoulos, FotisCampo Güerri, EliasStamatopoulos, KostasMartín-Subero, José Ignacio2023-12-112024-06-152023-06-151528-0020https://hdl.handle.net/2445/204390The chromatin activation landscape of chronic lymphocytic leukemia (CLL) with stereo-typed B-cell receptor immunoglobulin is currently unknown. In this study, we report the results of a whole-genome chromatin profiling of histone 3 lysine 27 acetylation of 22 CLLs from major subsets, which were compared against nonstereotyped CLLs and normal B-cell subpopulations. Although subsets 1, 2, and 4 did not differ much from their non-stereotyped CLL counterparts, subset 8 displayed a remarkably distinct chromatin acti-vation profile. In particular, we identified 209 de novo active regulatory elements in this subset, which showed similar patterns with U-CLLs undergoing Richter transformation. These regions were enriched for binding sites of 9 overexpressed transcription factors. In 78 of 209 regions, we identified 113 candidate overexpressed target genes, 11 regions being associated with more than 2 adjacent genes. These included blocks of up to 7 genes, suggesting local coupregulation within the same genome compartment. Our findings further underscore the uniqueness of subset 8 CLL, notable for the highest risk of Richter's transformation among all CLLs and provide additional clues to decipher the molecular basis of its clinical behavior.6 p.application/pdfeng(c) American Society of Hematology, 2023Leucèmia limfocítica crònicaCromatinaChronic lymphocytic leukemiaChromatininfo:eu-repo/semantics/article2023-11-30info:eu-repo/semantics/openAccess934957236989492