Epigenetic silencing and pharmacological inhibition of EIF5A2 foster venetoclax sensitivity in acute myeloid leukaemia

Br J Haematol. 2026 Apr;208(4):1437-1442. doi: 10.1111/bjh.70339. Epub 2026 Jan 28.

Abstract

We show how the loss of activity of the translation initiation factor EIF5A2-either through gene hypermethylation or pharmacologic inhibition of its highly specific hypusine post-translational modification-induces venetoclax sensitivity in acute myeloid leukaemia (AML) cells.

Keywords: DNA methylation; Epigenetics; acute myeloid leukemia; venetoclax.

MeSH terms

  • Antineoplastic Agents* / pharmacology
  • Antineoplastic Agents* / therapeutic use
  • Bridged Bicyclo Compounds, Heterocyclic* / pharmacology
  • Bridged Bicyclo Compounds, Heterocyclic* / therapeutic use
  • Cell Line, Tumor
  • DNA Methylation / drug effects
  • Drug Resistance, Neoplasm / drug effects
  • Drug Resistance, Neoplasm / genetics
  • Epigenesis, Genetic* / drug effects
  • Eukaryotic Translation Initiation Factor 5A
  • Gene Silencing*
  • Humans
  • Leukemia, Myeloid, Acute* / drug therapy
  • Leukemia, Myeloid, Acute* / genetics
  • Leukemia, Myeloid, Acute* / metabolism
  • Leukemia, Myeloid, Acute* / pathology
  • Peptide Initiation Factors* / antagonists & inhibitors
  • Peptide Initiation Factors* / genetics
  • Peptide Initiation Factors* / metabolism
  • RNA-Binding Proteins* / antagonists & inhibitors
  • RNA-Binding Proteins* / genetics
  • RNA-Binding Proteins* / metabolism
  • Sulfonamides* / pharmacology
  • Sulfonamides* / therapeutic use

Substances

  • Sulfonamides
  • Bridged Bicyclo Compounds, Heterocyclic
  • venetoclax
  • Eukaryotic Translation Initiation Factor 5A
  • Peptide Initiation Factors
  • RNA-Binding Proteins
  • Antineoplastic Agents