Skip to main page content
Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
. 2014 Nov;28(11):2222-8.
doi: 10.1038/leu.2014.130. Epub 2014 Apr 14.

Silencing AML1-ETO Gene Expression Leads to Simultaneous Activation of Both Pro-Apoptotic and Proliferation Signaling

Affiliations

Silencing AML1-ETO Gene Expression Leads to Simultaneous Activation of Both Pro-Apoptotic and Proliferation Signaling

P V Spirin et al. Leukemia. .

Abstract

The t(8;21)(q22;q22) rearrangement represents the most common chromosomal translocation in acute myeloid leukemia (AML). It results in a transcript encoding for the fusion protein AML1-ETO (AE) with transcription factor activity. AE is considered to be an attractive target for treating t(8;21) leukemia. However, AE expression alone is insufficient to cause transformation, and thus the potential of such therapy remains unclear. Several genes are deregulated in AML cells, including KIT that encodes a tyrosine kinase receptor. Here, we show that AML cells transduced with short hairpin RNA vector targeting AE mRNAs have a dramatic decrease in growth rate that is caused by induction of apoptosis and deregulation of the cell cycle. A reduction in KIT mRNA levels was also observed in AE-silenced cells, but silencing KIT expression reduced cell growth but did not induce apoptosis. Transcription profiling of cells that escape cell death revealed activation of a number of signaling pathways involved in cell survival and proliferation. In particular, we find that the extracellular signal-regulated kinase 2 (ERK2; also known as mitogen-activated protein kinase 1 (MAPK1)) protein could mediate activation of 23 out of 29 (79%) of these upregulated pathways and thus may be regarded as the key player in establishing the t(8;21)-positive leukemic cells resistant to AE suppression.

Similar articles

See all similar articles

Cited by 28 articles

See all "Cited by" articles

References

    1. Proc Natl Acad Sci U S A. 2011 Feb 8;108(6):2450-5 - PubMed
    1. Proc Natl Acad Sci U S A. 1998 Sep 1;95(18):10860-5 - PubMed
    1. Cancer Res. 1999 Jun 15;59(12):2766-9 - PubMed
    1. Cancer Res. 2006 Mar 15;66(6):2990-6 - PubMed
    1. Oncogene. 2001 Sep 10;20(40):5660-79 - PubMed

Publication types

MeSH terms

Substances

Feedback