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Chromatin activation profiling of stereotyped chronic lymphocytic leukemias reveals a subset 8-specific signature
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The 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.
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TSAGIOPOULOU, Maria, CHAPAPRIETA, Vicente, RUSSIÑOL, Nuria, GARCÍA TORRE, Beatriz, PECHLIVANIS, Nikolaos, NADEU PRAT, Ferran, PAPAKONSTANTINOU, Nikos, STAVROYIANNI, Niki, CHATZIDIMITRIOU, Anastasia, PSOMOPOULOS, Fotis, CAMPO GÜERRI, Elias, STAMATOPOULOS, Kostas, MARTÍN-SUBERO, José ignacio. Chromatin activation profiling of stereotyped chronic lymphocytic leukemias reveals a subset 8-specific signature. _Blood_. 2023. Vol. 141, núm. 24, pàgs. 2955-2960. [consulta: 24 de gener de 2026]. ISSN: 1528-0020. [Disponible a: https://hdl.handle.net/2445/204390]