While the role of NOTCH1 mutations in prognosis has not been established for several tumors and, for others, it remains unclear [6,7,15,16], PEST mutations identify a subset of lymphoproliferative disorders characterized by a poor prognosis, chemorefractoriness, and higher incidence of Richter’s transformation in the case of CLL [6,7,15,16,17]. This evidence concerns the gene NOTCH1 and lymphoproliferative syndrome.