Human Gene Set: DIAZ_CHRONIC_MYELOGENOUS_LEUKEMIA_DN


Standard name DIAZ_CHRONIC_MYELOGENOUS_LEUKEMIA_DN
Systematic name M17778
Brief description Genes down-regulated in CD34+ [GeneID=947] cells isolated from bone marrow of CML (chronic myelogenous leukemia) patients, compared to those from normal donors.
Full description or abstract In this study, we provide a molecular signature of highly enriched CD34+ cells from bone marrow of untreated patients with chronic myelogenous leukemia (CML) in chronic phase in comparison with normal CD34+ cells using microarrays covering 8746 genes. Expression data reflected several BCR-ABL-induced effects in primary CML progenitors, such as transcriptional activation of the classical mitogen-activated protein kinase pathway and the phosphoinositide-3 kinase/AKT pathway as well as downregulation of the proapoptotic gene IRF8. Moreover, novel transcriptional changes in comparison with normal CD34+ cells were identified. These include upregulation of genes involved in the transforming growth factorbeta pathway, fetal hemoglobin genes, leptin receptor, sorcin, tissue inhibitor of metalloproteinase 1, the neuroepithelial cell transforming gene 1 and downregulation of selenoprotein P. Additionally, genes associated with early hematopoietic stem cells (HSC) and leukemogenesis such as HoxA9 and MEIS1 were transcriptionally activated. Differential expression of differentiation-associated genes suggested an altered composition of the CD34+ cell population in CML. This was confirmed by subset analyses of chronic phase CML CD34+ cells showing an increase of the proportion of megakaryocyte-erythroid progenitors, whereas the proportion of HSC and granulocyte-macrophage progenitors was decreased in CML. In conclusion, our results give novel insights into the biology of CML and could provide the basis for identification of new therapeutic targets.
Collection C2: Curated
      CGP: Chemical and Genetic Perturbations
Source publication Pubmed 17252012   Authors: Diaz-Blanco E,Bruns I,Neumann F,Fischer JC,Graef T,Rosskopf M,Brors B,Pechtel S,Bork S,Koch A,Baer A,Rohr UP,Kobbe G,von Haeseler A,Gattermann N,Haas R,Kronenwett R
Exact source Table 2S: Fold Change < 1
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Organism Homo sapiens
Contributed by Leona Saunders (MSigDB Team)
Source platform AFFY_HG_U133
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Version history 7.5: Renamed from DIAZ_CHRONIC_MEYLOGENOUS_LEUKEMIA_DN

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