Skip to main page content
Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
. 2014 Apr;11(4):436-42.
doi: 10.1038/nmeth.2847. Epub 2014 Feb 23.

Identification of Small Molecules That Support Human Leukemia Stem Cell Activity Ex Vivo


Identification of Small Molecules That Support Human Leukemia Stem Cell Activity Ex Vivo

Caroline Pabst et al. Nat Methods. .


Leukemic stem cells (LSCs) are considered a major cause of relapse in acute myeloid leukemia (AML). Defining pathways that control LSC self-renewal is crucial for a better understanding of underlying mechanisms and for the development of targeted therapies. However, currently available culture conditions do not prevent spontaneous differentiation of LSCs, which greatly limits the feasibility of cell-based assays. To overcome these constraints we conducted a high-throughput chemical screen and identified small molecules that inhibit differentiation and support LSC activity in vitro. Similar to reports with cord blood stem cells, several of these compounds suppressed the aryl-hydrocarbon receptor (AhR) pathway, which we show to be inactive in vivo and rapidly activated ex vivo in AML cells. We also identified a compound, UM729, that collaborates with AhR suppressors in preventing AML cell differentiation. Together, these findings provide newly defined culture conditions for improved ex vivo culture of primary human AML cells.

Similar articles

See all similar articles

Cited by 34 articles

See all "Cited by" articles


    1. Science. 2010 Sep 10;329(5997):1345-8 - PubMed
    1. Proc Natl Acad Sci U S A. 2010 Dec 21;107(51):21990-5 - PubMed
    1. Cell Stem Cell. 2012 Feb 3;10(2):218-29 - PubMed
    1. Nature. 2011 Oct 05;478(7368):197-203 - PubMed
    1. Toxicology. 2008 Apr 18;246(2-3):112-23 - PubMed

Publication types

LinkOut - more resources