Skip Navigation
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.


The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Your Environment. Your Health.

Publication Detail

Title: A FOXO1-induced oncogenic network defines the AML1-ETO preleukemic program.

Authors: Lin, Shan; Ptasinska, Anetta; Chen, Xiaoting; Shrestha, Mahesh; Assi, Salam A; Chin, Paulynn S; Imperato, Maria R; Aronow, B J; Zhang, Jingsong; Weirauch, Matthew T; Bonifer, Constanze; Mulloy, James C

Published In Blood, (2017 09 07)

Abstract: Understanding and blocking the self-renewal pathway of preleukemia stem cells could prevent acute myeloid leukemia (AML) relapse. In this study, we show that increased FOXO1 represents a critical mechanism driving aberrant self-renewal in preleukemic cells expressing the t(8;21)-associated oncogene AML1-ETO (AE). Although generally considered as a tumor suppressor, FOXO1 is consistently upregulated in t(8;21) AML. Expression of FOXO1 in human CD34+ cells promotes a preleukemic state with enhanced self-renewal and dysregulated differentiation. The DNA binding domain of FOXO1 is essential for these functions. FOXO1 activates a stem cell molecular signature that is also present in AE preleukemia cells and preserved in t(8;21) patient samples. Genome-wide binding studies show that AE and FOXO1 share the majority of their binding sites, whereby FOXO1 binds to multiple crucial self-renewal genes and is required for their activation. In agreement with this observation, genetic and pharmacological ablation of FOXO1 inhibited the long-term proliferation and clonogenicity of AE cells and t(8;21) AML cell lines. Targeting of FOXO1 therefore provides a potential therapeutic strategy for elimination of stem cells at both preleukemic and leukemic stages.

PubMed ID: 28710059 Exiting the NIEHS site

MeSH Terms: Animals; Antigens, CD34/metabolism; Cell Line, Tumor; Cell Proliferation; Core Binding Factor Alpha 2 Subunit/genetics; Core Binding Factor Alpha 2 Subunit/metabolism*; Forkhead Box Protein O1/metabolism*; Gene Expression Profiling; Gene Expression Regulation, Leukemic; Gene Regulatory Networks*; Genome, Human; Hematopoietic Stem Cells/metabolism; Humans; Leukemia, Myeloid, Acute/genetics*; Leukemia, Myeloid, Acute/pathology; Mice, SCID; Oncogene Proteins, Fusion/genetics; Oncogene Proteins, Fusion/metabolism*; Precancerous Conditions/genetics*; Precancerous Conditions/pathology; RUNX1 Translocation Partner 1 Protein; Up-Regulation/genetics

to Top