STANDARD_NAME	AKL_HTLV1_INFECTION_UP
SYSTEMATIC_NAME	M7705
COLLECTION	C2:CGP
MSIGDB_URL	https://www.gsea-msigdb.org/gsea/msigdb/human/geneset/AKL_HTLV1_INFECTION_UP
NAMESPACE	AFFY_HG_U133
DESCRIPTION_BRIEF	Genes up-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.
DESCRIPTION_FULL	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.
PMID	17287851
GEOID	
AUTHORS	Akl H,Badran BM,Zein NE,Bex F,Sotiriou C,Willard-Gallo KE,Burny A,Martiat P
CONTRIBUTOR	Arthur Liberzon
CONTRIBUTOR_ORG	MSigDB Team
EXACT_SOURCE	Table 1S
FILTERED_BY_SIMILARITY	
EXTERNAL_NAMES_FOR_SIMILAR_TERMS	
EXTERNAL_DETAILS_URL	
SOURCE_MEMBERS	200602_at,200615_s_at,200872_at,201105_at,201251_at,201310_s_at,201416_at,201417_at,201518_at,201577_at,201830_s_at,202022_at,202345_s_at,202416_at,202546_at,203582_s_at,203695_s_at,205268_s_at,206571_s_at,208949_s_at,209576_at,210046_s_at,210337_s_at,210592_s_at,210844_x_at,213484_at,213540_at,214953_s_at,217995_at,218025_s_at
GENE_SYMBOLS	APP,AP2B1,S100A10,LGALS1,PKM,NREP,SOX4,SOX4,CBX1,NME1,NET1,ALDOC,FABP5,DNAJC7,VAMP8,RAB4A,GSDME,ADD2,MAP4K4,LGALS3,GNAI1,IDH2,ACLY,SAT1,CTNNA1,ADD2,HSD17B8,APP,SQOR,ECI2
FOUNDER_NAMES