Human Gene Set: GAL_LEUKEMIC_STEM_CELL_DN


Standard name GAL_LEUKEMIC_STEM_CELL_DN
Systematic name M4502
Brief description Genes down-regulated in leukemic stem cells (LSC), defined as CD34+CD38- [GeneID=947;952] cells from AML (acute myeloid leukemia patients) compared to the CD34+CD38+ cells.
Full description or abstract Tumors contain a fraction of cancer stem cells that maintain the propagation of the disease. The CD34(+)CD38(-) cells, isolated from acute myeloid leukemia (AML), were shown to be enriched leukemic stem cells (LSC). We isolated the CD34(+)CD38(-) cell fraction from AML and compared their gene expression profiles to the CD34(+)CD38(+) cell fraction, using microarrays. We found 409 genes that were at least twofold over- or underexpressed between the two cell populations. These include underexpression of DNA repair, signal transduction and cell cycle genes, consistent with the relative quiescence of stem cells, and chromosomal aberrations and mutations of leukemic cells. Comparison of the LSC expression data to that of normal hematopoietic stem cells (HSC) revealed that 34% of the modulated genes are shared by both LSC and HSC, supporting the suggestion that the LSC originated within the HSC progenitors. We focused on the Notch pathway since Jagged-2, a Notch ligand was found to be overexpressed in the LSC samples. We show that DAPT, an inhibitor of gamma-secretase, a protease that is involved in Jagged and Notch signaling, inhibits LSC growth in colony formation assays. Identification of additional genes that regulate LSC self-renewal may provide new targets for therapy.
Collection C2: Curated
      CGP: Chemical and Genetic Perturbations
Source publication Pubmed 17039238   Authors: Gal H,Amariglio N,Trakhtenbrot L,Jacob-Hirsh J,Margalit O,Avigdor A,Nagler A,Tavor S,Ein-Dor L,Lapidot T,Domany E,Rechavi G,Givol D
Exact source Table 4S: Under-expressed lists
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Source species Homo sapiens
Contributed by Leona Saunders (MSigDB Team)
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identifier namespace		 AFFY_HG_U133
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Version history 3.0: First introduced

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