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

Overview

Journal Nat Methods

Specialties Biomedical Engineering
Pathology

Date 2014 Feb 25

PMID 24562423

Citations 63

Authors

Caroline Pabst

Jana Krosl

Iman Fares

Genevieve Boucher

Rejean Ruel

Anne Marinier

Sebastien Lemieux

Josee Hebert

Guy Sauvageau

Affiliations

Soon will be listed here.

Abstract

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.

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