Insulin-like growth factor 1 receptor inhibits the proliferation of acute myeloid leukaemia cells via NK cell activation

Ann Hematol. 2023 Sep;102(9):2353-2364. doi: 10.1007/s00277-023-05378-0. Epub 2023 Jul 31.

Abstract

Acute myeloid leukaemia (AML) denotes a heterogeneous category of cancers occurring within the bone marrow that are initiated by the unrestricted proliferation of haematopoietic stem cells. Various factors effectuate the dysregulation of AML cell proliferation; for instance, the upregulation of insulin-like growth factor 1 receptor (IGF1R) within AML cells influences their proliferation. However, there is a current dearth of research assessing the association between IGF1R and prognostic risk as well as its potential as an AML immunotherapeutic. This study aims to elucidate the role of IGF1R in AML progression and evaluate its prognostic value. To this end, RNA-sequencing (RNA-seq) data from The Cancer Genome Atlas (TCGA) database was analysed to compare IGF1R expression between AML and normal tissues. Moreover, a Kaplan-Meier survival analysis was performed to determine whether IGF1R expression correlates with patient overall survival (OS). TCGA data revealed upregulated IGF1R expression in the peripheral blood of AML patients compared to that in healthy individuals. Meanwhile, IGF1R expression positively correlates with patient OS. Additionally, elevated IGF1R expression promotes NK cell expansion and enhances its functional activation, thereby inhibiting AML cell proliferation. Collectively, these findings highlight the clinical potential of IGF1R in the effective treatment of AML through the activation of NK cell proliferation and function and suggest that it may represent a potential predictive marker of AML prognosis.

Keywords: Acute myeloid leukaemia; Insulin-like growth factor 1 receptor; Natural killer cells; Therapeutic target.

MeSH terms

  • Cell Proliferation
  • Humans
  • Insulin-Like Growth Factor I*
  • Killer Cells, Natural
  • Leukemia, Myeloid, Acute* / genetics
  • Leukemia, Myeloid, Acute* / therapy
  • Prognosis
  • Treatment Outcome

Substances

  • Insulin-Like Growth Factor I
  • IGF1 protein, human