Insulin Growth Factor 1 Receptor Expression Is Associated with <i>NOTCH1</i> Mutation, Trisomy 12 and Aggressive Clinical Course in Chronic Lymphocytic Leukaemia

<div><p><i>IGF1R</i> is emerging as an important gene in the pathogenesis of many solid and haematological cancers and its over-expression has been reported as frequently associated with aggressive disease and chemotherapy resistance. In this study we performed an investigation of the role of <i>IGF1R</i> 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 <i>IGF1R</i> gene expression was significantly associated with <i>IGHV</i> unmutated (<i>IGHV</i>-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 <i>IGF1R</i> expression (p=0.002) characterized patients with <i>NOTCH1</i> mutation (c.7541_7542delCT), identified in 15.5% of cases of our series by next generation sequencing and ARMS-PCR. Furthermore, <i>IGF1R</i> expression has been proven as an independent prognostic factor associated with time to first treatment in our CLL prospective cohort. These data suggest that <i>IGF1R</i> may play an important role in CLL biology, in particular in aggressive CLL clones characterized by <i>IGHV</i>-UM, trisomy 12 and <i>NOTCH1</i> mutation.</p>