Format

Send to

Choose Destination
Blood. 2013 Mar 21;121(12):2289-300. doi: 10.1182/blood-2012-07-446120. Epub 2013 Jan 17.

Activity of a heptad of transcription factors is associated with stem cell programs and clinical outcome in acute myeloid leukemia.

Author information

1
Lowy Cancer Research Centre and the Prince of Wales Clinical School, University of New South Wales, Sydney, Australia.

Erratum in

  • Blood. 2014 May 1;123(18):2901.

Abstract

Aberrant transcriptional programs in combination with abnormal proliferative signaling drive leukemic transformation. These programs operate in normal hematopoiesis where they are involved in hematopoietic stem cell (HSC) proliferation and maintenance. Ets Related Gene (ERG) is a component of normal and leukemic stem cell signatures and high ERG expression is a risk factor for poor prognosis in acute myeloid leukemia (AML). However, mechanisms that underlie ERG expression in AML and how its expression relates to leukemic stemness are unknown. We report that ERG expression in AML is associated with activity of the ERG promoters and +85 stem cell enhancer and a heptad of transcription factors that combinatorially regulate genes in HSCs. Gene expression signatures derived from ERG promoter-stem cell enhancer and heptad activity are associated with clinical outcome when ERG expression alone fails. We also show that the heptad signature is associated with AMLs that lack somatic mutations in NPM1 and confers an adverse prognosis when associated with FLT3 mutations. Taken together, these results suggest that transcriptional regulators cooperate to establish or maintain primitive stem cell-like signatures in leukemic cells and that the underlying pattern of somatic mutations contributes to the development of these signatures and modulate their influence on clinical outcome.

PMID:
23327922
DOI:
10.1182/blood-2012-07-446120
[Indexed for MEDLINE]
Free full text

Publication type, MeSH terms, Substances, Grant support

Publication type

MeSH terms

Substances

Grant support

Supplemental Content

Full text links

Icon for HighWire
Loading ...
Support Center