Dysregulated gene expression networks in human acute myelogenous leukemia stem cells.
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.
Majeti
Ravindra
R
Institute for Stem Cell Biology and Regenerative Medicine and Department of Internal Medicine, Division of Hematology, Stanford University, Palo Alto, CA 94304, USA.
Becker
Michael W
MW
Tian
Qiang
Q
Lee
Tsung-Lu Michael
TL
Yan
Xiaowei
X
Liu
Rui
R
Chiang
Jung-Hsien
JH
Hood
Leroy
L
Clarke
Michael F
MF
Weissman
Irving L
IL
D030561:Databases, Nucleic Acid; D020869:Gene Expression Profiling; D015972:Gene Expression Regulation, Neoplastic / Q000235:genetics*; D053263:Gene Regulatory Networks / Q000235:genetics*; D006412:Hematopoietic Stem Cells / Q000378:metabolism; D006801:Humans; D015470:Leukemia, Myeloid, Acute / Q000235:genetics*; D014411:Neoplastic Stem Cells / Q000378:metabolism*