title: Insulin growth factor 1 receptor expression is associated with NOTCH1 mutation, trisomy 12 and aggressive clinical course in chronic lymphocytic leukaemia.
abstract: IGF1R 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 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 associated 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 NOTCH1 mutation (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 IGF1R may play an important role in CLL biology, in particular in aggressive CLL clones characterized by IGHV-UM, trisomy 12 and NOTCH1 mutation.
authors.affiliation: Department of Clinical Sciences and Community Health, University of Milano and Hematology 1 CTMO, Foundation IRCCS Ca' Granda, Ospedale Maggiore Policlinico, Milano, Italy.
authors.forename: Francesco
authors.initials: F
authors.lastname: Maura
authors.affiliation: Department of Clinical Sciences and Community Health, University of Milano and Hematology 1 CTMO, Foundation IRCCS Ca' Granda, Ospedale Maggiore Policlinico, Milano, Italy.
authors.forename: Laura
authors.initials: L
authors.lastname: Mosca
authors.affiliation: Department of Clinical Sciences and Community Health, University of Milano and Hematology 1 CTMO, Foundation IRCCS Ca' Granda, Ospedale Maggiore Policlinico, Milano, Italy.
authors.forename: Sonia
authors.initials: S
authors.lastname: Fabris
authors.affiliation: SS Molecular Diagnostics, IRCCS S. Martino-IST, Genova, Italy.
authors.forename: Giovanna
authors.initials: G
authors.lastname: Cutrona
authors.affiliation: Scientific Direction IRCCS S. Martino-IST, Genova, Italy.
authors.forename: Serena
authors.initials: S
authors.lastname: Matis
authors.affiliation: Department of Clinical Sciences and Community Health, University of Milano and Hematology 1 CTMO, Foundation IRCCS Ca' Granda, Ospedale Maggiore Policlinico, Milano, Italy.
authors.forename: Marta
authors.initials: M
authors.lastname: Lionetti
authors.affiliation: Department of Clinical Sciences and Community Health, University of Milano and Hematology 1 CTMO, Foundation IRCCS Ca' Granda, Ospedale Maggiore Policlinico, Milano, Italy.
authors.forename: Luca
authors.initials: L
authors.lastname: Agnelli
authors.affiliation: Department of Clinical Sciences and Community Health, University of Milano and Hematology 1 CTMO, Foundation IRCCS Ca' Granda, Ospedale Maggiore Policlinico, Milano, Italy.
authors.forename: Marzia
authors.initials: M
authors.lastname: Barbieri
authors.affiliation: Department of Clinical Sciences and Community Health, University of Milano and Hematology 1 CTMO, Foundation IRCCS Ca' Granda, Ospedale Maggiore Policlinico, Milano, Italy.
authors.forename: Marianna
authors.initials: M
authors.lastname: D'Anca
authors.affiliation: Department of Clinical Sciences and Community Health, University of Milano and Hematology 1 CTMO, Foundation IRCCS Ca' Granda, Ospedale Maggiore Policlinico, Milano, Italy.
authors.forename: Martina
authors.initials: M
authors.lastname: Manzoni
authors.affiliation: Scientific Direction IRCCS S. Martino-IST, Genova, Italy.
authors.forename: Monica
authors.initials: M
authors.lastname: Colombo
authors.affiliation: Scientific Direction IRCCS S. Martino-IST, Genova, Italy.
authors.forename: Carlotta
authors.initials: C
authors.lastname: Massucco
authors.affiliation: Department of Pathology IRCCS S. Martino-IST, Genova, Italy.
authors.forename: Daniele
authors.initials: D
authors.lastname: Reverberi
authors.affiliation: U.O.C. di Ematologia, Azienda Ospedaliera di Cosenza, Cosenza, Italy.
authors.forename: Massimo
authors.initials: M
authors.lastname: Gentile
authors.affiliation: U.O.C. di Ematologia, Azienda Ospedaliera di Cosenza, Cosenza, Italy.
authors.forename: Anna Grazia
authors.initials: AG
authors.lastname: Recchia
authors.affiliation: U.O.C. di Ematologia, Azienda Ospedaliera di Cosenza, Cosenza, Italy.
authors.forename: Sabrina
authors.initials: S
authors.lastname: Bossio
authors.affiliation: Division of Hematology, A.O. Arcispedale Santa Maria Nuova-IRCCS, Reggio Emilia, Italy.
authors.forename: Fiorella
authors.initials: F
authors.lastname: Ilariucci
authors.affiliation: Division of Haematology, University of Messina, Messina, Italy.
authors.forename: Caterina
authors.initials: C
authors.lastname: Musolino
authors.affiliation: Department of Biomedical Sciences, Division of Hematology, University of Catania and Ferrarotto Hospital, Catania, Italy.
authors.forename: Francesco
authors.initials: F
authors.lastname: Di Raimondo
authors.affiliation: Department of Clinical Sciences and Community Health, University of Milano and Hematology 1 CTMO, Foundation IRCCS Ca' Granda, Ospedale Maggiore Policlinico, Milano, Italy.
authors.forename: Agostino
authors.initials: A
authors.lastname: Cortelezzi
authors.affiliation: Department of Pathology IRCCS S. Martino-IST, Genova, Italy.
authors.forename: Fortunato
authors.initials: F
authors.lastname: Morabito
authors.affiliation: Scientific Direction IRCCS S. Martino-IST, Genova, Italy.
authors.forename: Manlio
authors.initials: M
authors.lastname: Ferrarini
authors.affiliation: Department of Clinical Sciences and Community Health, University of Milano and Hematology 1 CTMO, Foundation IRCCS Ca' Granda, Ospedale Maggiore Policlinico, Milano, Italy.
authors.forename: Antonino
authors.initials: A
authors.lastname: Neri
mesh_terms: D002881:Chromosomes, Human, Pair 12 / Q000235:genetics*; D002986:Clinical Trials as Topic; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D015451:Leukemia, Lymphocytic, Chronic, B-Cell / Q000175:diagnosis / Q000235:genetics* / Q000473:pathology; D009154:Mutation; D009367:Neoplasm Staging; D011379:Prognosis; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D017526:Receptor, IGF Type 1; D051881:Receptor, Notch1 / Q000235:genetics*; D017451:Receptors, Somatomedin / Q000235:genetics*; D014314:Trisomy / Q000235:genetics*
chemical_list: C000597236:IGF1R protein, human; D012333:RNA, Messenger; D051881:Receptor, Notch1; D017451:Receptors, Somatomedin; D017526:Receptor, IGF Type 1