Identification of FBXW7 mutations in untreated CLL patients. (A) In a total of 905 untreated CLL patients, 41 FBXW7 mutations were identified. The 3 different isoforms of FBXW7 have different N-termini (red boxes) but share the same dimerization (DD; green box), F-Box (blue box), and WD40 domains (purple box). Amino acid residues are numbered for the FBXW7α-isoform (AA (α)). Mutations are denoted by dots colored according to the alteration of the respective amino acid. (B) FBXW7α-isoform specific indel mutation result in the T15VR mutation within the nuclear localization signal (NLS). (C) Expression of the FBXW7α, -β, and -γ isoforms in 72 CLL patient samples relative to 3 housekeeping genes HPRT1, PPIA, and TBP. mRNA, messenger RNA.