IGF2BP2 promotes lncRNA DANCR stability mediated glycolysis and affects the progression of FLT3-ITD + acute myeloid leukemia

Apoptosis. 2023 Aug;28(7-8):1035-1047. doi: 10.1007/s10495-023-01846-0. Epub 2023 Apr 15.

Abstract

Internal tandem duplication (ITD) is the most common type of FLT3 mutation (FLT3-ITD), accounting for about 25% of AML patients. The expression of DANCR in FLT3-ITD AML had not been paid attention to, and whether its regulatory relationship with IGF2BP2 can affect the progression of FLT3-ITD AML was unclear. Our study sought to verify the biological role of IGF2BP2 as an m6A reading protein in FLT3-ITD AML. To further explore the role and mechanism of DANCR in AML, and provide a basis for the screening of biomarkers and the development of targeted drugs. The results show that IGF2BP2 was upregulated in FLT3-ITD+ AML patients and cells. Si-IGF2BP2 could inhibit the proliferation, glycolytic and promote the apoptosis in MV4-11 cells. IGF2BP2 could promote the DANCR RNA stability. This discovery will provide new horizons for early screening and targeted therapy of FLT3-ITD+ AML.

Keywords: Acute myeloid leukemia (AML); FLT3-ITD; Glycolysis; IGF2BP2; N6-methyladenosine.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Apoptosis / genetics
  • Biomarkers / metabolism
  • Glycolysis / genetics
  • Humans
  • Leukemia, Myeloid, Acute* / drug therapy
  • Mutation
  • RNA, Long Noncoding* / genetics
  • RNA, Long Noncoding* / metabolism
  • RNA-Binding Proteins / genetics
  • RNA-Binding Proteins / metabolism
  • fms-Like Tyrosine Kinase 3 / genetics
  • fms-Like Tyrosine Kinase 3 / metabolism
  • fms-Like Tyrosine Kinase 3 / therapeutic use

Substances

  • RNA, Long Noncoding
  • Biomarkers
  • fms-Like Tyrosine Kinase 3
  • FLT3 protein, human
  • IGF2BP2 protein, human
  • RNA-Binding Proteins