Cardiff University | Prifysgol Caerdydd ORCA
Online Research @ Cardiff 
WelshClear Cookie - decide language by browser settings

The AML1-ETO fusion gene promotes extensive self-renewal of human primary erythroid cells

Tonks, Alex, Pearn, Lorna, Tonks, Amanda Jayne, Pearce, Laurence, Hoy, Terence George, Phillips, Sarah, Fisher, Janet, Downing, James R., Burnett, Alan Kenneth and Darley, Richard Lawrence 2003. The AML1-ETO fusion gene promotes extensive self-renewal of human primary erythroid cells. Blood 101 (2) , pp. 624-632. 10.1182/blood-2002-06-1732

Full text not available from this repository.

Abstract

The t(8;21) translocation, which encodes the AML1-ETO fusion protein (now known as RUNX1-CBF2T1), is one of the most frequent translocations in acute myeloid leukemia, although its role in leukemogenesis is unclear. Here, we report that exogenous expression of AML1-ETO in human CD34+ cells severely disrupts normal erythropoiesis, resulting in virtual abrogation of erythroid colony formation. In contrast, in bulk liquid culture of purified erythroid cells, we found that while AML1-ETO initially inhibited proliferation during early (erythropoietin [EPO]-independent) erythropoiesis, growth inhibition gave way to a sustained EPO-independent expansion of early erythroid cells that continued for more than 60 days, whereas control cultures became growth arrested after 10 to 13 days (at the EPO-dependent stage of development). Phenotypic analysis showed that although these cells were CD13 and CD34, unlike control cultures, these cells failed to up-regulate CD36 or to down-regulate CD33, suggesting that expression of AML1-ETO suppressed the differentiation of these cells and allowed extensive self-renewal to occur. In the early stages of this expansion, addition of EPO was able to promote both phenotypic (CD36+, CD33, glycophorin A+) and morphologic differentiation of these cells, almost as effectively as in control cultures. However, with extended culture, cells expressing AML1-ETO became refractory to addition of this cytokine, suggesting that a block in differentiation had been established. These data demonstrate the capacity of AML1-ETO to promote the self-renewal of human hematopoietic cells and therefore support a causal role for t(8;21) translocations in leukemogenesis.

Item Type: Article
Date Type: Publication
Status: Published
Schools: Medicine
Subjects: R Medicine > R Medicine (General)
ISSN: 15280020
Last Modified: 25 Jun 2017 01:31
URI: http://orca.cf.ac.uk/id/eprint/358

Citation Data

Cited 57 times in Google Scholar. View in Google Scholar

Cited 42 times in Scopus. View in Scopus. Powered By Scopus® Data

Actions (repository staff only)

Edit Item Edit Item