Fig 4. Rationale for DFMO- and specific genetic and metabolic markers of DFMO effect, in neuroblastoma.

. ODC transcription is influenced by specific genetic variability, including the SNPs rs2302615 [19, 22] and rs2302616 [24]. The DFMO target ODC decarboxylates ornithine to form the diamine putrescine, which is then metabolized into longer chain amines. Spermidine is a substrate for two acetyltransferases that monoacetylate this amine at either the N¹ or N⁸ positions. Spermine is a substrate for one of these transferases (SAT1), which diacetylates this amine. Putrescine, the monoacetylspermidines and diacetylspermine are all substrates for the solute carrier transporter SLC3A2/Y+LAT, which exports these amines.