{"owner": "ArrayExpress Uploader", "ownerprofile_id": "arrayexpress_sid", "species": "mouse", "factors": [{"GSM861215": {"DISEASE STAGE": "not specified", "TIME OF TAMOXIFEN TREATMENT": "7 months of tamoxifen treatment in vivo", "ORGANISM PART": "bone marrow", "CELLULAR STATE": "high proliferation state with low DDR signaling"}}, {"GSM861215": {"DISEASE STAGE": "not specified", "TIME OF TAMOXIFEN TREATMENT": "7 months of tamoxifen treatment in vivo", "ORGANISM PART": "bone marrow", "CELLULAR STATE": "high proliferation state with low DDR signaling"}}, {"GSM861215": {"DISEASE STAGE": "not specified", "TIME OF TAMOXIFEN TREATMENT": "7 months of tamoxifen treatment in vivo", "ORGANISM PART": "bone marrow", "CELLULAR STATE": "high proliferation state with low DDR signaling"}}, {"GSM861215": {"DISEASE STAGE": "not specified", "TIME OF TAMOXIFEN TREATMENT": "7 months of tamoxifen treatment in vivo", "ORGANISM PART": "bone marrow", "CELLULAR STATE": "high proliferation state with low DDR signaling"}}, {"GSM861219": {"DISEASE STAGE": "not specified", "TIME OF TAMOXIFEN TREATMENT": "from 7 to 8 months of tamoxifen treatment in vivo", "ORGANISM PART": "bone marrow", "CELLULAR STATE": "the transition period of lower proliferation and high DDR activity"}}, {"GSM861219": {"DISEASE STAGE": "not specified", "TIME OF TAMOXIFEN TREATMENT": "from 7 to 8 months of tamoxifen treatment in vivo", "ORGANISM PART": "bone marrow", "CELLULAR STATE": "the transition period of lower proliferation and high DDR activity"}}, {"GSM861219": {"DISEASE STAGE": "not specified", "TIME OF TAMOXIFEN TREATMENT": "from 7 to 8 months of tamoxifen treatment in vivo", "ORGANISM PART": "bone marrow", "CELLULAR STATE": "the transition period of lower proliferation and high DDR activity"}}, {"GSM861219": {"DISEASE STAGE": "not specified", "TIME OF TAMOXIFEN TREATMENT": "from 7 to 8 months of tamoxifen treatment in vivo", "ORGANISM PART": "bone marrow", "CELLULAR STATE": "the transition period of lower proliferation and high DDR activity"}}, {"GSM861223": {"DISEASE STAGE": "not specified", "TIME OF TAMOXIFEN TREATMENT": "8 months of tamoxifen treatment in vivo", "ORGANISM PART": "bone marrow", "CELLULAR STATE": "senescence"}}, {"GSM861223": {"DISEASE STAGE": "not specified", "TIME OF TAMOXIFEN TREATMENT": "8 months of tamoxifen treatment in vivo", "ORGANISM PART": "bone marrow", "CELLULAR STATE": "senescence"}}, {"GSM861223": {"DISEASE STAGE": "not specified", "TIME OF TAMOXIFEN TREATMENT": "8 months of tamoxifen treatment in vivo", "ORGANISM PART": "bone marrow", "CELLULAR STATE": "senescence"}}, {"GSM861226": {"DISEASE STAGE": "not specified", "TIME OF TAMOXIFEN TREATMENT": "8 months of tamoxifen treatment in vivo", "ORGANISM PART": "bone marrow", "CELLULAR STATE": "not specified"}}, {"GSM861227": {"DISEASE STAGE": "not specified", "TIME OF TAMOXIFEN TREATMENT": "7 months of tamoxifen treatment in vivo", "ORGANISM PART": "bone marrow", "CELLULAR STATE": "not specified"}}, {"GSM861227": {"DISEASE STAGE": "not specified", "TIME OF TAMOXIFEN TREATMENT": "7 months of tamoxifen treatment in vivo", "ORGANISM PART": "bone marrow", "CELLULAR STATE": "not specified"}}, {"GSM861227": {"DISEASE STAGE": "not specified", "TIME OF TAMOXIFEN TREATMENT": "7 months of tamoxifen treatment in vivo", "ORGANISM PART": "bone marrow", "CELLULAR STATE": "not specified"}}, {"GSM861230": {"DISEASE STAGE": "early - induced proliferation and DDR", "TIME OF TAMOXIFEN TREATMENT": "7 months of tamoxifen treatment in vivo", "ORGANISM PART": "spleen", "CELLULAR STATE": "not specified"}}, {"GSM861230": {"DISEASE STAGE": "early - induced proliferation and DDR", "TIME OF TAMOXIFEN TREATMENT": "7 months of tamoxifen treatment in vivo", "ORGANISM PART": "spleen", "CELLULAR STATE": "not specified"}}, {"GSM861230": {"DISEASE STAGE": "early - induced proliferation and DDR", "TIME OF TAMOXIFEN TREATMENT": "7 months of tamoxifen treatment in vivo", "ORGANISM PART": "spleen", "CELLULAR STATE": "not specified"}}, {"GSM861233": {"DISEASE STAGE": "progression - partial senescence and DDR is maintained", "TIME OF TAMOXIFEN TREATMENT": "10 months of tamoxifen treatment in vivo", "ORGANISM PART": "spleen", "CELLULAR STATE": "not specified"}}, {"GSM861233": {"DISEASE STAGE": "progression - partial senescence and DDR is maintained", "TIME OF TAMOXIFEN TREATMENT": "10 months of tamoxifen treatment in vivo", "ORGANISM PART": "spleen", "CELLULAR STATE": "not specified"}}, {"GSM861235": {"DISEASE STAGE": "progression - partial senescence and DDR is maintained", "TIME OF TAMOXIFEN TREATMENT": "9 months of tamoxifen treatment in vivo", "ORGANISM PART": "spleen", "CELLULAR STATE": "not specified"}}, {"GSM861236": {"DISEASE STAGE": "terminal stage - proliferation, low or absent DDR and no senescence", "TIME OF TAMOXIFEN TREATMENT": "21 months of tamoxifen treatment in vivo", "ORGANISM PART": "spleen", "CELLULAR STATE": "not specified"}}, {"GSM861237": {"DISEASE STAGE": "terminal stage - proliferation, low or absent DDR and no senescence", "TIME OF TAMOXIFEN TREATMENT": "23 months of tamoxifen treatment in vivo", "ORGANISM PART": "spleen", "CELLULAR STATE": "not specified"}}, {"GSM861238": {"DISEASE STAGE": "terminal stage - proliferation, low or absent DDR and no senescence", "TIME OF TAMOXIFEN TREATMENT": "19 months of tamoxifen treatment in vivo", "ORGANISM PART": "spleen", "CELLULAR STATE": "not specified"}}, {"GSM861239": {"DISEASE STAGE": "not specified", "TIME OF TAMOXIFEN TREATMENT": "24 months of tamoxifen treatment in vivo", "ORGANISM PART": "spleen", "CELLULAR STATE": "not specified"}}, {"GSM861240": {"DISEASE STAGE": "not specified", "TIME OF TAMOXIFEN TREATMENT": "8 months of tamoxifen treatment in vivo", "ORGANISM PART": "spleen", "CELLULAR STATE": "not specified"}}, {"GSM86124": {"DISEASE STAGE": "not specified", "TIME OF TAMOXIFEN TREATMENT": "9 months of tamoxifen treatment in vivo", "ORGANISM PART": "spleen", "CELLULAR STATE": "not specified"}}, {"GSM861242": {"DISEASE STAGE": "not specified", "TIME OF TAMOXIFEN TREATMENT": "11 months of tamoxifen treatment in vivo", "ORGANISM PART": "spleen", "CELLULAR STATE": "not specified"}}, {"GSM861242": {"DISEASE STAGE": "not specified", "TIME OF TAMOXIFEN TREATMENT": "11 months of tamoxifen treatment in vivo", "ORGANISM PART": "spleen", "CELLULAR STATE": "not specified"}}], "id": 8601, "pop_total": 0, "platform": 8, "summary_wrapped": "Activation of the MLL-ENL-ERtm oncogene initiates aberrant proliferation of myeloid progenitors. Here, we show induction of a fail-safe...", "pubmed_id": 22516260, "geo_gse_id": "E-GEOD-35038", "owner_profile": "/profile/8773/arrayexpressuploader", "factor_count": 4, "sample_count": 29, "tags": ["acute leukemia", "bone", "bone marrow", "cancer", "cell", "disease", "estrogen", "leukemia", "myeloproliferative disease", "protein", "spleen", "stem cell"], "lastmodified": "Dec.12, 2014", "is_default": false, "geo_gds_id": "", "slug": "dna-damage-response-and-inflammatory-signaling-lim", "geo_id_plat": "E-GEOD-35038_A-AFFY-36", "name": "DNA Damage Response and Inflammatory Signaling Limit the MLL-ENL-induced Leukemogenesis in vivo", "created": "Nov.24, 2014", "summary": "Activation of the MLL-ENL-ERtm oncogene initiates aberrant proliferation of myeloid progenitors. Here, we show induction of a fail-safe mechanism mediated by the DNA damage response (DDR) machinery that results in activation of the ATR/ATM-Chk1/Chk2-p53/p21 checkpoint and cellular senescence at early stages of cellular transformation caused by a regulatable MLL-ENL-ERtm in mice. Furthermore, we identified the transcription program underlying this intrinsic anti-cancer barrier, and DDR-induced inflammatory regulators that fine-tune the signaling towards senescence, thereby modulating the fate of MLL-ENL-immortalized cells in a tissue-environment-dependent manner. Our results indicate that DDR is a rate-limiting event for acquisition of stem cell-like properties in MLL-ENL-ERtm-mediated transformation, as experimental inhibition of the barrier accelerated the transition to immature cell states and acute leukemia development. We created a mouse model wherein the protein function of the MLL-ENL oncogene depends on tamoxifen due to fusion with the mutated estrogen-binding domain of the estrogen receptor (ERtm). After 7 months of tamoxifen administration, the MLL-ENL-ERtm mice developed a myeloproliferative disease, which progressed into the terminal stage after a long period (mean survival: 592 \u00b1 112 days) of continuous tamoxifen provision. We have profiled gene expression at three time-points of tamoxifen treatment corresponding to three distinct cellular states of the MLL-ENL-ERtm-induced myeloproliferation in the bone marrow: 1. 7 months - high proliferation state with low DDR signaling (4 biological replicates), 2. 7-8 months - the transition period of lower proliferation and high DDR activity (4 biogical replicates) and 3. 8 months - the senescence (3 biological replicates). Time-matched tamoxifen-treated wild-type bone marrow analysed in 4 biological replicates. We have profiled gene expression in three disease stages in the spleen: 1. 7 months - early stage - induced proliferation and DDR (3 biological replicates), 2. 9-10 months - progression - partial senescence and DDR is maintained (3 biological replicates) and 3. 16-23 months - terminal stage - proliferation, low or absent DDR and no senescence (3 biological replicates). Time-matched tamoxifen-treated and age-matched wild-type spleens analysed in 5 biological replicates.", "source": "http://www.ebi.ac.uk/arrayexpress/experiments/E-GEOD-35038", "sample_source": "http://www.ebi.ac.uk/arrayexpress/experiments/E-GEOD-35038/samples/"}