Dysregulated gene expression networks in human acute myelogenous leukemia stem cells

Ravindra Majeti, Michael W. Becker, Qiang Tian, Tsung Lu Michael Lee, Xiaowei Yan, Rui Liu, Jung Hsien Chiang, Leroy Hood, Michael F. Clarke, Irving L. Weissman

Research output: Contribution to journalArticlepeer-review

201 Citations (Scopus)

Abstract

We performed the first genome-wide expression analysis directly comparing the expression profile of highly enriched normal human hematopoietic stem cells (HSC) and leukemic stem cells (LSC) from patients with acute myeloid leukemia (AML). Comparing the expression signature of normal HSC to that of LSC, we identified 3,005 differentially expressed genes. Using 2 independent analyses, we identified multiple pathways that are aberrantly regulated in leukemic stem cells compared with normal HSC. Several pathways, including Wnt signaling, MAP Kinase signaling, and Adherens Junction, are well known for their role in cancer development and stem cell biology. Other pathways have not been previously implicated in the regulation of cancer stem cell functions, including Ribosome and T Cell Receptor Signaling pathway. This study demonstrates that combining global gene expression analysis with detailed annotated pathway resources applied to highly enriched normal and malignant stem cell populations, can yield an understanding of the critical pathways regulating cancer stem cells.

Original languageEnglish
Pages (from-to)3396-3401
Number of pages6
JournalProceedings of the National Academy of Sciences of the United States of America
Volume106
Issue number9
DOIs
Publication statusPublished - 2009 Mar 3

All Science Journal Classification (ASJC) codes

  • General

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