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<MSIGDB BUILD_DATE="Jan 29, 2026" VERSION="2026.1.Hs" NAME="export">
    <GENESET STANDARD_NAME="GSE8685_IL2_STARVED_VS_IL2_ACT_IL2_STARVED_CD4_TCELL_DN" SYSTEMATIC_NAME="M325" HISTORICAL_NAMES="" PMID="18281483" AUTHORS="Marzec M,Halasa K,Kasprzycka M,Wysocka M,Liu X,Tobias JW,Baldwin D,Zhang Q,Odum N,Rook AH,Wasik MA" GEOID="GSE8685" EXACT_SOURCE="GSE8685_3173_200_DN" GENESET_LISTING_URL="" EXTERNAL_DETAILS_URL="" CHIP="HUMAN_GENE_SYMBOL" CONTRIBUTOR="Jernej Godec" CONTRIBUTOR_ORG="Dana-Farber Cancer Institute" DESCRIPTION_BRIEF="Genes down-regulated in Sez-2 cells (T cell lymphoma): untreated versus IL2 [GeneID=3558]." DESCRIPTION_FULL="In this study we compared the effects of IL-2, IL-15, and IL-21 on the gene expression, activation of cell signaling pathways, and functional properties of cells derived from the CD4+ cutaneous T-cell lymphoma (CTCL). Whereas both IL-2 and IL-15 that signal through receptors that share the common gamma chain and the beta chain modulated the expression of &gt;1,000 genes, IL-21 that signals via the receptor also containing gamma chain up-regulated &lt;40 genes. All three cytokines induced tyrosine phosphorylation of Jak1 and Jak3. However, only IL-2 and IL-15 strongly activated STAT5, PI3K/Akt, and MEK/ERK signaling pathways. In contrast, IL-21 selectively activated STAT3. Whereas all three cytokines protected CTCL cells from apoptosis, only IL-2 and IL-15 promoted their proliferation. The effects of the cytokine stimulation were Jak3- and Jak1-kinase dependent. These findings document the vastly different impact of IL-2 and IL-15 vs. IL-21 on malignant CD4+ T cells. They also suggest two novel therapeutic approaches to CTCL and, possibly, other CD4+ T cell lymphomas: inhibition of the Jak1/Jak3 kinase complex and, given the known strong immunostimulatory properties of IL-21 on CD8+ T, NK, and B cells, application of this cytokine to boost an immune response against malignant CD4+ T cells." TAGS="" MEMBERS="ABCC4,ADAM9,AGL,ALDH2,API5,ASF1B,BID,BRI3BP,BSN,C11orf74,C12orf42,C15orf43,C16orf58,C17orf53,C1GALT1C1,C4orf19,C6orf170,C6orf48,C6orf62,C9orf82,CACNA1D,CCDC137,CCDC18,CCDC34,CCNA2,CDC14A,CDCA2,CDH1,CDK2AP1,CENPM,CES5A,CKAP2,CKAP2L,CLTA,CNNM2,CPNE2,CREG2,CRELD2,CSF3R,CSTF3,CTC1,DAGLB,DBI,DCLRE1B,DEPDC1,DEPTOR,DHX9,DKC1,DNMT1,DOCK1,DOLK,DTWD1,EEPD1,EIF4H,ELANE,EME1,ENOPH1,ERLIN1,ERLIN2,ESCO2,FADS2,FAM111A,FAM184A,FAM98B,FANCB,FNIP1,FRRS1,FUCA2,FUT8,G6PD,GAB2,GABRP,GANC,GCLM,GFI1,GLIPR1,GMDS,GMPR,GORASP2,GOT2,H2AFY,HDLBP,HMGA2,HNRNPU,HPSE,HSD17B1,ICA1,IDH3A,IKBKAP,IL11RA,IL15,IL1R1,IMPA1,IMPDH2,IREB2,KBTBD13,KIAA1549,KIFAP3,KPNA2,KPNB1,KRR1,KRTAP2-4,LEO1,LOC155060,LRRC58,LUC7L3,MANEA,MAPK7,MAPK8,MDM1,MED6,MEIS1,MIER3,MIS18BP1,MMP2,MORF4L1,MOSPD2,MTM1,NAT8L,NEDD4,NEK2,NEO1,NPM1,NUP43,OAF,OAZ1,PARL,PCM1,PDE6D,PHLDB2,PKIB,POLA2,POLR1A,POLR1D,PRIM2,PSME4,PXT1,QTRTD1,RAB11FIP5,RACGAP1,RAD54B,RAI14,RBM44,RELL1,RFWD3,RNASEH2B,RNF144B,RNF157,RNF7,RPGR,RRM1,SCML2,SCOC,SDF2L1,SEC23B,SEC24D,SEPHS1,SEPHS2,SERBP1,SERPINF1,SH3D19,SKA3,SLC22A3,SLC31A1,SNHG3,SNORD47,SNX9,SOX12,SPAG5,SPNS2,SRD5A1,SRRM1,SSX2IP,STX3,TBC1D24,TBC1D2B,THG1L,TIMELESS,TKT,TM6SF1,TMEM144,TMEM38B,TMEM8B,TOMM6,TRIM35,TWISTNB,TYMS,UBE2Q2,UGDH,UMOD,UNC5B,USP11,VAPA,WHSC1,ZBED5,ZDHHC5,ZFP41,ZNF330,ZNF446,ZWILCH" MEMBERS_SYMBOLIZED="ABCC4,ADAM9,AGL,ALDH2,API5,ASF1B,BID,BRI3BP,BSN,C12orf42,C1GALT1C1,C6orf62,CAAP1,CACNA1D,CCDC137,CCDC18,CCDC34,CCNA2,CDC14A,CDCA2,CDH1,CDK2AP1,CENPM,CES5A,CKAP2,CKAP2L,CLTA,CNNM2,CPNE2,CREG2,CRELD2,CSF3R,CSTF3,CTC1,DAGLB,DBI,DCLRE1B,DEPDC1,DEPTOR,DHX9,DKC1,DNMT1,DOCK1,DOLK,DTWD1,EEPD1,EIF4H,ELANE,ELP1,EME1,ENOPH1,ERLIN1,ERLIN2,ESCO2,FADS2,FAM111A,FAM184A,FAM98B,FANCB,FNIP1,FRRS1,FUCA2,FUT8,G6PD,GAB2,GABRP,GANC,GCLM,GFI1,GLIPR1,GMDS,GMPR,GORASP2,GOT2,HDLBP,HMGA2,HNRNPU,HPSE,HROB,HSD17B1,ICA1,IDH3A,IFTAP,IL11RA,IL15,IL1R1,IMPA1,IMPDH2,IREB2,KBTBD13,KIAA1549,KIFAP3,KPNA2,KPNB1,KRR1,KRTAP2-4,LEO1,LRRC58,LUC7L3,MACROH2A1,MANEA,MAPK7,MAPK8,MDM1,MED6,MEIS1,MIER3,MIS18BP1,MMP2,MORF4L1,MOSPD2,MTM1,NAT8L,NEDD4,NEK2,NEO1,NPM1,NSD2,NUP43,OAF,OAZ1,PARL,PCM1,PDE6D,PGCKA1,PHLDB2,PKIB,POLA2,POLR1A,POLR1D,POLR1F,PRIM2,PSME4,PXT1,QTRT2,RAB11FIP5,RACGAP1,RAD54B,RAI14,RBM44,RELL1,RFWD3,RNASEH2B,RNF144B,RNF157,RNF7,RPGR,RRM1,RUSF1,SCML2,SCOC,SDF2L1,SEC23B,SEC24D,SEPHS1,SEPHS2,SERBP1,SERPINF1,SH3D19,SKA3,SLC22A3,SLC31A1,SNHG3,SNHG32,SNX9,SOX12,SPAG5,SPNS2,SRD5A1,SRRM1,SSX2IP,STX3,TBC1D24,TBC1D2B,TBC1D32,TERB2,THG1L,TIMELESS,TKT,TM6SF1,TMEM144,TMEM38B,TMEM8B,TOMM6,TRIM35,TYMS,UBE2Q2,UGDH,UMOD,UNC5B,USP11,VAPA,ZBED5,ZDHHC5,ZFP41,ZNF330,ZNF446,ZWILCH" MEMBERS_EZID="10001,100188893,10250,10257,10389,10483,10613,10615,10855,10933,11010,11103,11160,114804,116064,117178,119710,1211,123169,124976,1317,140707,1441,145645,146956,1479,150468,152503,157313,157570,158747,1622,1660,166968,1736,178,1786,1793,1991,200407,217,2187,219699,220323,221150,221184,221223,221322,221830,221955,222659,22845,22920,22928,22929,23087,23102,23198,23649,23753,2519,2530,2539,255488,2568,25788,25885,25921,2595,26003,26056,26064,26135,26586,2672,2730,27309,2762,2766,2806,283742,286128,29071,29127,3069,3192,3292,3382,339230,339983,3419,343099,348995,3554,3590,3600,3612,3615,3658,374470,375316,3837,3838,390594,391059,4211,4313,4534,4734,4751,4756,4869,4946,50854,5108,51082,51429,5147,51747,51754,5176,53346,54805,54974,55055,55151,55159,55286,55314,55320,55486,5558,55635,55663,5570,55723,5598,5599,56890,56986,57465,57670,58478,58486,60592,6103,6240,637,63901,64755,64798,64858,6581,6666,6715,6809,7086,7298,7358,7369,7458,7468,768211,776,78995,79019,79174,79621,79632,79691,79694,79886,80169,80820,8091,8099,81688,8237,8420,8518,85294,8539,8556,8754,890,8914,8927,90102,91057,9218,92912,9415,9555,9616,96459,9846,9871,999" MEMBERS_MAPPING="ABCC4,ABCC4,10257|ADAM9,ADAM9,8754|AGL,AGL,178|ALDH2,ALDH2,217|API5,API5,8539|ASF1B,ASF1B,55723|BID,BID,637|BRI3BP,BRI3BP,140707|BSN,BSN,8927|C11orf74,IFTAP,119710|C12orf42,C12orf42,374470|C15orf43,TERB2,145645|C16orf58,RUSF1,64755|C17orf53,HROB,78995|C1GALT1C1,C1GALT1C1,29071|C4orf19,PGCKA1,55286|C6orf170,TBC1D32,221322|C6orf48,SNHG32,50854|C6orf62,C6orf62,81688|C9orf82,CAAP1,79886|CACNA1D,CACNA1D,776|CCDC137,CCDC137,339230|CCDC18,CCDC18,343099|CCDC34,CCDC34,91057|CCNA2,CCNA2,890|CDC14A,CDC14A,8556|CDCA2,CDCA2,157313|CDH1,CDH1,999|CDK2AP1,CDK2AP1,8099|CENPM,CENPM,79019|CES5A,CES5A,221223|CKAP2,CKAP2,26586|CKAP2L,CKAP2L,150468|CLTA,CLTA,1211|CNNM2,CNNM2,54805|CPNE2,CPNE2,221184|CREG2,CREG2,200407|CRELD2,CRELD2,79174|CSF3R,CSF3R,1441|CSTF3,CSTF3,1479|CTC1,CTC1,80169|DAGLB,DAGLB,221955|DBI,DBI,1622|DCLRE1B,DCLRE1B,64858|DEPDC1,DEPDC1,55635|DEPTOR,DEPTOR,64798|DHX9,DHX9,1660|DKC1,DKC1,1736|DNMT1,DNMT1,1786|DOCK1,DOCK1,1793|DOLK,DOLK,22845|DTWD1,DTWD1,56986|EEPD1,EEPD1,80820|EIF4H,EIF4H,7458|ELANE,ELANE,1991|EME1,EME1,146956|ENOPH1,ENOPH1,58478|ERLIN1,ERLIN1,10613|ERLIN2,ERLIN2,11160|ESCO2,ESCO2,157570|FADS2,FADS2,9415|FAM111A,FAM111A,63901|FAM184A,FAM184A,79632|FAM98B,FAM98B,283742|FANCB,FANCB,2187|FNIP1,FNIP1,96459|FRRS1,FRRS1,391059|FUCA2,FUCA2,2519|FUT8,FUT8,2530|G6PD,G6PD,2539|GAB2,GAB2,9846|GABRP,GABRP,2568|GANC,GANC,2595|GCLM,GCLM,2730|GFI1,GFI1,2672|GLIPR1,GLIPR1,11010|GMDS,GMDS,2762|GMPR,GMPR,2766|GORASP2,GORASP2,26003|GOT2,GOT2,2806|H2AFY,MACROH2A1,9555|HDLBP,HDLBP,3069|HMGA2,HMGA2,8091|HNRNPU,HNRNPU,3192|HPSE,HPSE,10855|HSD17B1,HSD17B1,3292|ICA1,ICA1,3382|IDH3A,IDH3A,3419|IKBKAP,ELP1,8518|IL11RA,IL11RA,3590|IL15,IL15,3600|IL1R1,IL1R1,3554|IMPA1,IMPA1,3612|IMPDH2,IMPDH2,3615|IREB2,IREB2,3658|KBTBD13,KBTBD13,390594|KIAA1549,KIAA1549,57670|KIFAP3,KIFAP3,22920|KPNA2,KPNA2,3838|KPNB1,KPNB1,3837|KRR1,KRR1,11103|KRTAP2-4,KRTAP2-4,85294|LEO1,LEO1,123169|LOC155060,null,null|LRRC58,LRRC58,116064|LUC7L3,LUC7L3,51747|MANEA,MANEA,79694|MAPK7,MAPK7,5598|MAPK8,MAPK8,5599|MDM1,MDM1,56890|MED6,MED6,10001|MEIS1,MEIS1,4211|MIER3,MIER3,166968|MIS18BP1,MIS18BP1,55320|MMP2,MMP2,4313|MORF4L1,MORF4L1,10933|MOSPD2,MOSPD2,158747|MTM1,MTM1,4534|NAT8L,NAT8L,339983|NEDD4,NEDD4,4734|NEK2,NEK2,4751|NEO1,NEO1,4756|NPM1,NPM1,4869|NUP43,NUP43,348995|OAF,OAF,220323|OAZ1,OAZ1,4946|PARL,PARL,55486|PCM1,PCM1,5108|PDE6D,PDE6D,5147|PHLDB2,PHLDB2,90102|PKIB,PKIB,5570|POLA2,POLA2,23649|POLR1A,POLR1A,25885|POLR1D,POLR1D,51082|PRIM2,PRIM2,5558|PSME4,PSME4,23198|PXT1,PXT1,222659|QTRTD1,QTRT2,79691|RAB11FIP5,RAB11FIP5,26056|RACGAP1,RACGAP1,29127|RAD54B,RAD54B,25788|RAI14,RAI14,26064|RBM44,RBM44,375316|RELL1,RELL1,768211|RFWD3,RFWD3,55159|RNASEH2B,RNASEH2B,79621|RNF144B,RNF144B,255488|RNF157,RNF157,114804|RNF7,RNF7,9616|RPGR,RPGR,6103|RRM1,RRM1,6240|SCML2,SCML2,10389|SCOC,SCOC,60592|SDF2L1,SDF2L1,23753|SEC23B,SEC23B,10483|SEC24D,SEC24D,9871|SEPHS1,SEPHS1,22929|SEPHS2,SEPHS2,22928|SERBP1,SERBP1,26135|SERPINF1,SERPINF1,5176|SH3D19,SH3D19,152503|SKA3,SKA3,221150|SLC22A3,SLC22A3,6581|SLC31A1,SLC31A1,1317|SNHG3,SNHG3,8420|SNORD47,null,null|SNX9,SNX9,51429|SOX12,SOX12,6666|SPAG5,SPAG5,10615|SPNS2,SPNS2,124976|SRD5A1,SRD5A1,6715|SRRM1,SRRM1,10250|SSX2IP,SSX2IP,117178|STX3,STX3,6809|TBC1D24,TBC1D24,57465|TBC1D2B,TBC1D2B,23102|THG1L,THG1L,54974|TIMELESS,TIMELESS,8914|TKT,TKT,7086|TM6SF1,TM6SF1,53346|TMEM144,TMEM144,55314|TMEM38B,TMEM38B,55151|TMEM8B,TMEM8B,51754|TOMM6,TOMM6,100188893|TRIM35,TRIM35,23087|TWISTNB,POLR1F,221830|TYMS,TYMS,7298|UBE2Q2,UBE2Q2,92912|UGDH,UGDH,7358|UMOD,UMOD,7369|UNC5B,UNC5B,219699|USP11,USP11,8237|VAPA,VAPA,9218|WHSC1,NSD2,7468|ZBED5,ZBED5,58486|ZDHHC5,ZDHHC5,25921|ZFP41,ZFP41,286128|ZNF330,ZNF330,27309|ZNF446,ZNF446,55663|ZWILCH,ZWILCH,55055" FILTERED_BY_SIMILARITY="" FOUNDER_NAMES="" REFINEMENT_DATASETS="" VALIDATION_DATASETS="" CATEGORY_CODE="C7" ORGANISM="Homo sapiens" SUB_CATEGORY_CODE="IMMUNESIGDB"/>
</MSIGDB>
