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. 2009 Mar 3;106(9):3396-401.
doi: 10.1073/pnas.0900089106. Epub 2009 Feb 13.

Dysregulated gene expression networks in human acute myelogenous leukemia stem cells

Ravindra Majeti  1 , Michael W Becker, Qiang Tian, Tsung-Lu Michael Lee, Xiaowei Yan, Rui Liu, Jung-Hsien Chiang, Leroy Hood, Michael F Clarke, Irving L Weissman
Affiliations

Dysregulated gene expression networks in human acute myelogenous leukemia stem cells

Ravindra Majeti et al. Proc Natl Acad Sci U S A. .

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.

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Conflict of interest statement

Conflict of interest statement: I.L.W. was a member of the scientific advisory board of Amgen and owns significant Amgen stock. I.L.W. cofounded and consulted for Systemix, is a cofounder and director of Stem Cells Inc., and cofounded Cellerant, Inc. L.H. is a scientific founder of Integrated Diagnostics, a protein diagnostics company using blood, and Amgen, a large biotechnology company.

Figures

Fig. 1.
Fig. 1.
Schematic representation of dysregulated pathway identification.
Fig. 2.
Fig. 2.
Visualization of molecular interaction and reaction networks in the KEGG database. (A) Adherens junction. (B) Wnt signaling pathway. Red color represents up-regulation in LSC, green color represents up-regulation in HSC, and yellow color represents no significant change.
Fig. 3.
Fig. 3.
Functional Groups Association Networks (FGAN) visualized using the Cytoscape program. Each node represents 1 enriched functional group (GO molecular function, GO cellular component, and Swissprot keywords) with P value <0.02 performed by DAVID. A total of 3005 differentially expressed genes were evaluated by the functional enrichment analysis. The size of the node is proportional to the number of genes in each functional group. The largest functional group is the protein kinase activity of GO molecular function, which contains 103 genes. The edge width represents the number of shared genes between any two functional groups.
See this image and copyright information in PMC

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