Proteomic analysis identifies differentially expressed proteins in AML1/ETO acute myeloid leukemia cells treated with DNMT inhibitors azacitidine and decitabine.
Azacitidine and decitabine are DNA methyltransferase inhibitors used to treat myelodysplastic syndromes and acute myeloid leukemias. To further characterize different mechanisms between these two agents, cellular extracts from leukemic cells untreated or treated with either drug were analyzed using 2D electrophoresis. Numerous differentially expressed proteins were identified with MALDI-TOF/TOF-MS. Cyclophilin A, Catalase, Nucleophosmin and PCNA were decreased exclusively by azacitidine, TCP1 and hnRNP A2/B1 by both drugs; alpha-Enolase and Peroxiredoxin-1 by decitabine. Interestingly, the expression of the proinflammatory protein Cyclophilin A, also suggested as marker of cell necrosis, was stimulated by decitabine. Finally, a comprehensive pathway analysis of data highlighted a relationship between the identified proteins and potential effectors.
Functional Unit of Hematology, University of Florence, Florence, Italy.
Francesca
F
Buchi
Elena
E
Spinelli
Erico
E
Masala
Antonella
A
Gozzini
Alessandro
A
Sanna
Alberto
A
Bosi
Germano
G
Ferrari
Valeria
V
Santini
D001374:Azacitidine / Q000031:analogs & derivatives* / Q000627:therapeutic use*; D050676:Core Binding Factor Alpha 2 Subunit / Q000235:genetics*; D015254:DNA Modification Methylases / Q000037:antagonists & inhibitors*; D000077209:Decitabine; D004791:Enzyme Inhibitors / Q000627:therapeutic use*; D006801:Humans; D015470:Leukemia, Myeloid, Acute / Q000188:drug therapy* / Q000235:genetics / Q000378:metabolism; D015514:Oncogene Proteins, Fusion / Q000235:genetics*; D040901:Proteomics / Q000379:methods*; D000075142:RUNX1 Translocation Partner 1 Protein
C107844:AML1-ETO fusion protein, human; D050676:Core Binding Factor Alpha 2 Subunit; D004791:Enzyme Inhibitors; D015514:Oncogene Proteins, Fusion; D000075142:RUNX1 Translocation Partner 1 Protein; D000077209:Decitabine; D015254:DNA Modification Methylases; D001374:Azacitidine