Various factors contribute to Richter transformation, including aberrant NOTCH1 signaling, increased c-MYC activity, and deletions and mutations of CDKN2A and TP53, as well as CLL subset 8, characterized by a specific chromatin activation pattern and transcription factor activity. CDKN2A, cyclin-dependent kinase inhibitor 2A; H3K27ac, histone 3 lysine 27 acetylation; KLF15, Krüppel-like factor 15; MYF6, myogenic factor 6; NICD, Notch intracellular domain; ZBTB7A, zinc finger and BTB domain-containing protein 7A; ZNF467, zinc finger protein 467.