> Details

Balabanov, Stefan; Gontarewicz, Artur; Ziegler, Patrick; Hartmann, Ulrike; Kammer, Winfried; Copland, Mhairi; Brassat, Ute; Priemer, Martin; Hauber, Ilona; Wilhelm, Thomas; Schwarz, Gerold; Kanz, Lothar; Bokemeyer, Carsten; Hauber, Joachim; Holyoake, Tessa L.; Nordheim, Alfred; Brümmendorf, Tim H.

Hypusination of eukaryotic initiation factor 5A (eIF5A): a novel therapeutic target in BCR-ABL–positive leukemias identified by a proteomics approach

Reference
management

Bookmarks

Remove from
bookmarks

Share this on Whatsapp

Close

Bookmarks



You can manage bookmarks using lists, please log in to your user account for this.
  • Media type: E-Article
  • Title: Hypusination of eukaryotic initiation factor 5A (eIF5A): a novel therapeutic target in BCR-ABL–positive leukemias identified by a proteomics approach
  • Contributor: Balabanov, Stefan; Gontarewicz, Artur; Ziegler, Patrick; Hartmann, Ulrike; Kammer, Winfried; Copland, Mhairi; Brassat, Ute; Priemer, Martin; Hauber, Ilona; Wilhelm, Thomas; Schwarz, Gerold; Kanz, Lothar; Bokemeyer, Carsten; Hauber, Joachim; Holyoake, Tessa L.; Nordheim, Alfred; Brümmendorf, Tim H.
  • imprint: American Society of Hematology, 2007
  • Published in: Blood
  • Language: English
  • DOI: 10.1182/blood-2005-03-037648
  • ISSN: 0006-4971; 1528-0020
  • Keywords: Cell Biology ; Hematology ; Immunology ; Biochemistry
  • Origination:
  • Footnote:
  • Description: <jats:title>Abstract</jats:title><jats:p>Inhibition of BCR-ABL tyrosine kinase with imatinib represents a major breakthrough in the treatment of patients with chronic myeloid leukemia (CML). However, resistance to imatinib develops frequently, particularly in late-stage disease. To identify new cellular BCR-ABL downstream targets, we analyzed differences in global protein expression in BCR-ABL–positive K562 cells treated with or without imatinib in vitro. Among the 19 proteins found to be differentially expressed, we detected the down-regulation of eukaryotic initiation factor 5A (eIF5A), a protein essential for cell proliferation. eIF5A represents the only known eukaryotic protein activated by posttranslational hypusination. Hypusination inhibitors (HIs) alone exerted an antiproliferative effect on BCR-ABL–positive and –negative leukemia cell lines in vitro. However, the synergistic dose-response relationship found for the combination of imatinib and HI was restricted to Bcr-Abl–positive cells. Furthermore, this synergistic effect was confirmed by cytotoxicity assays, cell-cycle analysis, and CFSE labeling of primary CD34+ CML cells. Specificity of this effect could be demonstrated by cotreatment of K562 cells with imatinib and siRNA against eIF5. In conclusion, through a comparative proteomics approach and further functional analysis, we identified the inhibition of eIF5A hypusination as a promising new approach for combination therapy in BCR-ABL–positive leukemias.</jats:p>
  • Access State: Open Access