Our results showed that mutations of four genes (EGR2, FBXW7, RPS15, and FOXO1) were directly related to shorter TFS, and six genes (NOTCH1, ATM, GNA12, KDM6A, KMT2A, and FBXW7) were linked to four clinical factors associated with shorter TFS, including CLL-IPI, del(11q), splenomegaly, and newly diagnosed platelets <100 × 109/L. This evidence concerns the gene RPS15 and Splenomegaly.