RESEARCH ARTICLE Insulin Growth Factor 1 Receptor Expression Is Associated with NOTCH1Mutation, Trisomy 12 and Aggressive Clinical Course in

IGF1R is emerging as an important gene in the pathogenesis of many solid and haematolo-gical cancers and its over-expression has been reported as frequently associated with ag-gressive disease and chemotherapy resistance. In this study we performed an investigation of the role of IGF1R expression in a large and representative prospective series of 217 chronic lymphocytic leukaemia (CLL) patients enrolled in the multicentre O-CLL1 protocol (clinicaltrial.gov #NCT00917540). High IGF1R gene expression was significantly associat-ed with IGHV unmutated (IGHV-UM) status (p<0.0001), high CD38 expression (p<0.0001), trisomy 12 (p<0.0001), and del(11)(q23) (p=0.014). Interestingly, higher IGF1R expression (p=0.002) characterized patients with NOTCH1mutation (c.7541_7542delCT), identified in 15.5 % of cases of our series by next generation sequencing and ARMS-PCR. Furthermore, IGF1R expression has been proven as an independent prognostic factor associated with time to first treatment in our CLL prospective cohort. These data suggest that IGF1Rmay play an important role in CLL biology, in particular in aggressive CLL clones characterize