Dysregulated gene expression networks in human acute myelogenous leukemia stem cells

  • Ravindra Majeti
    Institute for Stem Cell Biology and Regenerative Medicine and Department of Internal Medicine, Divisions of Hematology and Oncology, Stanford University, Palo Alto, CA 94304;
  • Michael W. Becker
    Division of Hematology/Oncology, University of Rochester, Rochester, NY 14627;
  • Qiang Tian
    Institute for Systems Biology, Seattle, WA 98103;
  • Tsung-Lu Michael Lee
    Institute for Systems Biology, Seattle, WA 98103;
  • Xiaowei Yan
    Institute for Systems Biology, Seattle, WA 98103;
  • Rui Liu
    University of Michigan School of Dentistry, Ann Arbor, MI 48109
  • Jung-Hsien Chiang
    Institute for Systems Biology, Seattle, WA 98103;
  • Leroy Hood
    Institute for Systems Biology, Seattle, WA 98103;
  • Michael F. Clarke
    Institute for Stem Cell Biology and Regenerative Medicine and Department of Internal Medicine, Divisions of Hematology and Oncology, Stanford University, Palo Alto, CA 94304;
  • Irving L. Weissman
    Institute for Stem Cell Biology and Regenerative Medicine and Department of Internal Medicine, Divisions of Hematology and Oncology, Stanford University, Palo Alto, CA 94304;

書誌事項

公開日
2009-03-03
DOI
  • 10.1073/pnas.0900089106
公開者
Proceedings of the National Academy of Sciences

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説明

<jats:p>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.</jats:p>

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