2011
DOI: 10.1182/blood.v118.21.55.55
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Abstract: 55 Recurrent chromosomal translocations involving the mixed lineage leukaemia (MLL) gene initiate aggressive forms of leukaemia, which confer a poor prognosis and are often refractory to conventional therapies. Recent efforts have begun to unravel the molecular pathogenesis of these malignancies. Several groups have demonstrated that MLL-fusions associate with two macromolecular chromatin complexes; the polymerase associated factor (PAFc) complex, which interacts with the N-terminal domain of ML… Show more

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Cited by 273 publications
(507 citation statements)
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“…First, we found that I-BET151 inhibits LPS-induced expression of CXCL10, CXCL11, and IFNB in a dose-and time-dependent manner in human macrophages ( Fig. 1A-C), which confirms previous results in mouse BM-derived macrophages [31]. I-BET151 also suppressed TNF-induced CXCL10 and CXCL11 expression in a dose-dependent manner, and effectively suppressed TNF-induced IFNB expression ( Fig.…”
Section: Introductionsupporting
confidence: 89%
“…First, we found that I-BET151 inhibits LPS-induced expression of CXCL10, CXCL11, and IFNB in a dose-and time-dependent manner in human macrophages ( Fig. 1A-C), which confirms previous results in mouse BM-derived macrophages [31]. I-BET151 also suppressed TNF-induced CXCL10 and CXCL11 expression in a dose-dependent manner, and effectively suppressed TNF-induced IFNB expression ( Fig.…”
Section: Introductionsupporting
confidence: 89%
“…Recruits CDK9 to chromatin Mutated in ovarian cancer [105] Changes in activity affect metastatic properties in breast cancer [102][103][104] Inhibition decreases hematological malignancy [99][100][101]…”
Section: Brd4mentioning
confidence: 99%
“…Knockdown of BRD2, 3, or 4 proteins, however, results in reduced expression of multiple inflammatory cytokines in macrophages suggesting all three BET proteins control the transcription of inflammatory genes in LPS-stimulated macrophages [26]. This is likely through the ability of BRD2, BRD3, and BRD4 to interact with the PAF1 (polymerase associated factor 1) complex, or other chromatin modifying proteins such as NSD3 or JMJD6 [31].…”
Section: Histone Acetylationmentioning
confidence: 99%
“…also prevented LPS-induced endotoxic shock and bacteria-induced sepsis in mice [26], highlighting its potential as an antiinflammatory agent. A second class of BET family bromodomain inhibitor, I-BET151, with improved pharmacokinetics [31] was also shown to reduce levels of circulating IL-6 and protected mice from LPS-induced death [133]. Independent studies using an alternative pan-BET inhibitor, JQ1, also observed suppression of proinflammatory cytokine induction, and rescued mice from LPS-induced death [26,134].…”
Section: Bet Inhibitors As Antiinflammatory Agentsmentioning
confidence: 99%