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Proteomic analysis identifies differentially expressed proteins in AML1/ETO acute myeloid leukemia cells treated with DNMT inhibitors azacitidine and decitabine.

Abstract
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.
AuthorsFrancesca Buchi, Elena Spinelli, Erico Masala, Antonella Gozzini, Alessandro Sanna, Alberto Bosi, Germano Ferrari, Valeria Santini
JournalLeukemia research (Leuk Res) Vol. 36 Issue 5 Pg. 607-18 (May 2012) ISSN: 1873-5835 [Electronic] England
PMID22230298 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
CopyrightCopyright © 2011 Elsevier Ltd. All rights reserved.
Chemical References
  • AML1-ETO fusion protein, human
  • Core Binding Factor Alpha 2 Subunit
  • Enzyme Inhibitors
  • Oncogene Proteins, Fusion
  • RUNX1 Translocation Partner 1 Protein
  • Decitabine
  • DNA Modification Methylases
  • Azacitidine
Topics
  • Azacitidine (analogs & derivatives, therapeutic use)
  • Core Binding Factor Alpha 2 Subunit (genetics)
  • DNA Modification Methylases (antagonists & inhibitors)
  • Decitabine
  • Enzyme Inhibitors (therapeutic use)
  • Humans
  • Leukemia, Myeloid, Acute (drug therapy, genetics, metabolism)
  • Oncogene Proteins, Fusion (genetics)
  • Proteomics (methods)
  • RUNX1 Translocation Partner 1 Protein

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