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Insulin growth factor 1 receptor expression is associated with NOTCH1 mutation, trisomy 12 and aggressive clinical course in chronic lymphocytic leukaemia.

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  • معلومة اضافية
    • المصدر:
      Publisher: Public Library of Science Country of Publication: United States NLM ID: 101285081 Publication Model: eCollection Cited Medium: Internet ISSN: 1932-6203 (Electronic) Linking ISSN: 19326203 NLM ISO Abbreviation: PLoS One Subsets: MEDLINE
    • بيانات النشر:
      Original Publication: San Francisco, CA : Public Library of Science
    • الموضوع:
      Gene Expression Regulation, Neoplastic* ; Mutation*; Chromosomes, Human, Pair 12/*genetics ; Leukemia, Lymphocytic, Chronic, B-Cell/*genetics ; Receptor, Notch1/*genetics ; Receptors, Somatomedin/*genetics ; Trisomy/*genetics; Clinical Trials as Topic ; Humans ; Leukemia, Lymphocytic, Chronic, B-Cell/diagnosis ; Leukemia, Lymphocytic, Chronic, B-Cell/pathology ; Neoplasm Staging ; Prognosis ; RNA, Messenger/genetics ; RNA, Messenger/metabolism ; Receptor, IGF Type 1
    • نبذة مختصرة :
      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.
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    • Molecular Sequence:
      GEO GSE51529
      ClinicalTrials.gov NCT00917540
    • الرقم المعرف:
      0 (IGF1R protein, human)
      0 (RNA, Messenger)
      0 (Receptor, Notch1)
      0 (Receptors, Somatomedin)
      EC 2.7.10.1 (Receptor, IGF Type 1)
    • الموضوع:
      Date Created: 20150319 Date Completed: 20160201 Latest Revision: 20201209
    • الموضوع:
      20221213
    • الرقم المعرف:
      PMC4365018
    • الرقم المعرف:
      10.1371/journal.pone.0118801
    • الرقم المعرف:
      25786252