TY  - JOUR
A1  - Bartel, Yvonne
A1  - Grez, Manuel
A1  - Wichmann, Christian
T1  - Interference with RUNX1/ETO leukemogenic function by cell-penetrating peptides targeting the NHR2 oligomerization domain
T2  - BioMed research international, volume 2013, article id 297692
N2  - 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.
Y1  - 2013
UR  - http://publikationen.ub.uni-frankfurt.de/frontdoor/index/index/docId/32978
UR  - https://nbn-resolving.org/urn:nbn:de:hebis:30:3-329785
N1  - Copyright © 2013 Yvonne Bartel et al. This is an open access article distributed under the Creative Commons Attribution License http://creativecommons.org/licenses/by/3.0/ , which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
VL  - 2013
IS  - Article ID 297692
SP  - 1
EP  - 14
PB  - Hindawi
CY  - New York [u.a.]
ER  -