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E-GEOD-34044 - Gene expression profiles of AML derived stem cells: similarity to hematopoietic stem cells

Status
Released on 1 December 2011, last updated on 15 December 2011
Organism
Homo sapiens
Samples (8)
Array (1)
Protocols (7)
Description
Tumors contain a fraction of cancer stem cells that maintain the propagation of the disease. The CD34‏CD38_ cells, isolated from acute myeloid leukemia (AML), were shown to be enriched leukemic stem cells (LSC). We isolated the CD34‏CD38_ cell fraction from AML and compared their gene expression profiles to the CD34‏CD38‏ 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. Microarrays were used to compare the gene expression patterns between AML CD34+CD38- cells and AML CD34+CD38+
Experiment type
transcription profiling by array 
Contacts
jasmine jacob <j-jacob@sheba.health.gov.il>, A Avigdor, Aharon Nagler, David Givol, Eitan Domani, Gideon Rechavi, Hila Gal, Jasmine Jacob-Hirsch, L Ein-Dor, Luba Trakhtenbrot, Ninette Amariglio, Ofer Margalit, Sigal Tavor, T Lapidot
MIAME
PlatformsProtocolsVariablesProcessedRaw
Files
Investigation descriptionE-GEOD-34044.idf.txt
Sample and data relationshipE-GEOD-34044.sdrf.txt
Raw data (1)E-GEOD-34044.raw.1.zip
Processed data (1)E-GEOD-34044.processed.1.zip
Array designA-AFFY-37.adf.txt
Links