About: DNA Damage Response and Inflammatory Signaling Limit the MLL-ENL-Induced Leukemogenesis In Vivo

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rdf:type	skos:Concept http://linked.opendata.cz/ontology/domain/vavai/Vysledek
Description	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(CIP1) 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 anticancer barrier, and DDR-induced inflammatory regulators that fine-tune the signaling toward 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. 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(CIP1) 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 anticancer barrier, and DDR-induced inflammatory regulators that fine-tune the signaling toward 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. (en)
Title	DNA Damage Response and Inflammatory Signaling Limit the MLL-ENL-Induced Leukemogenesis In Vivo DNA Damage Response and Inflammatory Signaling Limit the MLL-ENL-Induced Leukemogenesis In Vivo (en)
skos:prefLabel	DNA Damage Response and Inflammatory Signaling Limit the MLL-ENL-Induced Leukemogenesis In Vivo DNA Damage Response and Inflammatory Signaling Limit the MLL-ENL-Induced Leukemogenesis In Vivo (en)
skos:notation	RIV/61989592:15110/12:33139786!RIV13-MZ0-15110___
http://linked.open...avai/predkladatel	Lékařská fakulta
http://linked.open...avai/riv/aktivita	P Z
http://linked.open...avai/riv/aktivity	P(2B06077), P(GA301/01/0489), P(IAA501370902), P(NS10282), Z(MSM0021620806), Z(MSM6198959205), Z(MSM6198959216)
http://linked.open...iv/cisloPeriodika	4
http://linked.open...vai/riv/dodaniDat	2013
http://linked.open...aciTvurceVysledku	Bártek, Jiří DOLEŽEL, Petr LUŽNÁ, Pavla DIVOKÝ, Vladimír
http://linked.open.../riv/druhVysledku	J - Článek v odborném periodiku
http://linked.open...iv/duvernostUdaju	S - Úplné a pravdivé údaje nepodléhající ochraně podle zvláštních právních předpisů
http://linked.open...titaPredkladatele	Univerzita Palackého v Olomouci / Lékařská fakulta
http://linked.open...dnocenehoVysledku	131759
http://linked.open...ai/riv/idVysledku	RIV/61989592:15110/12:33139786
http://linked.open...riv/jazykVysledku	eng - angličtina
http://linked.open.../riv/klicovaSlova	Leukemogenesis; Anticancer Barrier; Cellular Senescence; Inflammatory Signaling; DNA Damage Response; MLL-ENL-ERtm Oncogene (en)
http://linked.open.../riv/klicoveSlovo	Anticancer Barrier Cellular Senescence DNA Damage Response Inflammatory Signaling Leukemogenesis MLL-ENL-ERtm Oncogene
http://linked.open...odStatuVydavatele	US - Spojené státy americké
http://linked.open...ontrolniKodProRIV	[28B08B9E53E2]
http://linked.open...i/riv/nazevZdroje	Cancer Cell
http://linked.open...in/vavai/riv/obor	FD
http://linked.open...ichTvurcuVysledku	4 (xsd:int)
http://linked.open...cetTvurcuVysledku	8 (xsd:int)
http://linked.open...vavai/riv/projekt	High throughput analysis of chromatin structure for development of novel diagnostic and therapeutic approaches in cancer. Genomic integrity and instability mechanisms in the pathogenesis and potential personalized targeted treatment of prostate cancer. The study of pathogenesis of acute leukemias (AL) with 11q23 chromosomal rearrangement Cellular responses to replication stress: Mechanisms and the role of fragile sites in genomic instability
http://linked.open...UplatneniVysledku	2012
http://linked.open...v/svazekPeriodika	21
http://linked.open...iv/tvurceVysledku	Bártek, Jiří Doležel, Petr Bartkova, Jiřina Divoký, Vladimír Stranecky, Viktor Lužná, Pavla Slany, Robert Takáčová, Sylvia
http://linked.open...ain/vavai/riv/wos	000303187400009
http://linked.open...n/vavai/riv/zamer	Molekulární biologie a patologie buňky za normy a u vybraných klinicky závažných patologických procesů Studies of genes and molecular mechanisms involved in regulation of hematopoiesis, their clinical impact and targeted treatment Modulation of signalling and regulatory pathways in normal and cancer cells
issn	1535-6108
number of pages	15 (xsd:int)
http://bibframe.org/vocab/doi	10.1016/j.ccr.2012.01.021
http://localhost/t...ganizacniJednotka	15110
is http://linked.open...avai/riv/vysledek of	DNA Damage Response and Inflammatory Signaling Limit the MLL-ENL-Induced Leukemogenesis In Vivo

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