Gene Set: AKL_HTLV1_INFECTION_DN

Standard name AKL_HTLV1_INFECTION_DN
Systematic name M9815
Brief description Genes down-regulated in WE17/10 cells (CD4+ [GeneID=920] T lymphocytes) infected by HTLV1 (and thus displaying low CD7 [GeneID=924]) compared to the uninfected (i.e., CD7+) cells.
Full description or abstract Adult T-cell leukemia/lymphoma (ATLL) is a malignancy slowly emerging from human T-cell leukemia virus type 1 (HTLV-I)-infected mature CD4(+) T-cells. To characterize the molecular modifications induced by HTLV-I infection, we compared HTLV-I-infected WE17/10 cells with control cells, using micro-arrays. Many calcium-related genes were progressively downmodulated over a period of 2 years. Infected cells acquired a profound decrease of intracellular calcium levels in response to ionomycin, timely correlated with decreased CD7 expression. Focusing on apoptosis-related genes and their relationship with CD7, we observed an underexpression of most antiapoptotic genes. Western blotting revealed increasing Akt and Bad phosphorylation, timely correlated with CD7 loss. This was shown to be phosphatidylinositol 3-kinase (PI3K)-dependent. Activation of PI3K/Akt induced resistance to the apoptotic effect of interleukin-2 deprivation. We thus propose the following model: HTLV-I infection induces a progressive decrease in CD3 genes expression, which eventually abrogates CD3 expression; loss of CD3 is known to perturb calcium transport. This perturbation correlates with loss of CD7 expression and induction of Akt and Bad phosphorylation via activation of PI3K. The activation of the Akt/Bad pathway generates a progressive resistance to apoptosis, at a time HTLV-I genes expression is silenced, thus avoiding immune surveillance. This could be a major event in the process of the malignant transformation into ATLL.
Collection C2: curated gene sets
      CGP: chemical and genetic perturbations
Source publication Pubmed 17287851   Authors: Akl H,Badran BM,Zein NE,Bex F,Sotiriou C,Willard-Gallo KE,Burny A,Martiat P
Exact source Table 1S
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Organism Homo sapiens
Contributed by Arthur Liberzon (Broad Institute)
Source platform HG-U133A
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Compendia expression profiles Human tissue compendium (Novartis)
NCI-60 cell lines (National Cancer Institute)
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Version history 3.0: First introduced

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