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

PloS One
Francesco MauraAntonino Neri

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.

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Citations

Feb 26, 2016·Nature Reviews. Cancer·Giulia Fabbri, Riccardo Dalla-Favera
Jun 21, 2019·Epigenetics : Official Journal of the DNA Methylation Society·Subazini Thankaswamy KosalaiMeena Kanduri
Sep 24, 2016·Oncotarget·Deeksha VishwamitraHesham M Amin
Jul 3, 2015·The Journal of Immunology : Official Journal of the American Association of Immunologists·Patricia K A MonginiNicholas Chiorazzi
Mar 21, 2017·Proceedings of the National Academy of Sciences of the United States of America·Giulia FabbriRiccardo Dalla-Favera
Nov 14, 2020·Journal of Cellular Physiology·Mohammadreza MoonesiHanie Mehdizadeh

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Datasets Mentioned

BETA
GSE51529

Methods Mentioned

BETA
flow cytometry
Assay
PCR

Clinical Trials Mentioned

NCT00917540

Software Mentioned

R

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