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BioMed Research International
Volume 2013 (2013), Article ID 297692, 14 pages
http://dx.doi.org/10.1155/2013/297692
Research Article

Interference with RUNX1/ETO Leukemogenic Function by Cell-Penetrating Peptides Targeting the NHR2 Oligomerization Domain

1Institute for Biomedical Research, Georg-Speyer-Haus, 60596 Frankfurt, Germany
2Institute for Molecular Medicine, Goethe-University, 60590 Frankfurt, Germany
3Department of Transfusion Medicine, Cell Therapy and Haemostasis, Ludwig-Maximilian University Hospital, 81377 Munich, Germany

Received 22 February 2013; Revised 9 June 2013; Accepted 10 June 2013

Academic Editor: Lubna Nasir

Copyright © 2013 Yvonne Bartel et al. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

Abstract

The leukemia-associated fusion protein RUNX1/ETO is generated by the chromosomal translocation t(8;21) which appears in about 12% of all de novo acute myeloid leukemias (AMLs). Essential for the oncogenic potential of RUNX1/ETO is the oligomerization of the chimeric fusion protein through the nervy homology region 2 (NHR2) within ETO. In previous studies, we have shown that the intracellular expression of peptides containing the NHR2 domain inhibits RUNX1/ETO oligomerization, thereby preventing cell proliferation and inducing differentiation of RUNX1/ETO transformed cells. Here, we show that introduction of a recombinant TAT-NHR2 fusion polypeptide into the RUNX1/ETO growth-dependent myeloid cell line Kasumi-1 results in decreased cell proliferation and increased numbers of apoptotic cells. This effect was highly specific and mediated by binding the TAT-NHR2 peptide to ETO sequences, as TAT-polypeptides containing the oligomerization domain of BCR did not affect cell proliferation or apoptosis in Kasumi-1 cells. Thus, the selective interference with NHR2-mediated oligomerization by peptides represents a challenging but promising strategy for the inhibition of the leukemogenic potential of RUNX1/ETO in t(8;21)-positive leukemia.