Polycomb group (PcG) proteins assemble to form large multiprotein complexes involved in gene silencing. Evidence suggests that PcG complexes are heterogeneous with respect to both protein composition and speci®c function. MPc3 is a recently described mouse Polycomb (Pc) protein that shares structural homology with at least two other Pc proteins, M33 and MPc2. All three Pc proteins bind another PcG protein, RING1, through a conserved carboxy-terminal C-box motif. Here, data are presented demonstrating that MPc3 also interacts with AF9, a transcriptional activator implicated in the development of acute leukemias. The carboxy-terminus of AF9 is fused to the MLL protein in leukemias characterized by t(9;11)(p22;q23) chromosomal translocations. Importantly, it is the carboxy-terminus of AF9 to which MPc3 binds. The AF9 binding site of MPc3 maps to a central, non-conserved, region of the polypeptide sequence. In contrast to MPc3, data indicate that the Pc protein M33 does not interact with AF9. This ®nding suggests a potentially unique role for MPc3 in linking a PcG silencing complex to a transcriptional activator protein. Oncogene (2001) 20, 3798 ± 3805.

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2016-12-24T18:13:07

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INTRODUCTION: Favorable safety and effectiveness outcomes were presented previously for the Neuroform Atlas Stent following the completion of its pre-market study (ATLAS trial [Safety and Effectiveness of the Treatment of Wide Neck, Saccular, Intracranial Aneurysms with the Neuroform Atlas Stent System]) in anterior and posterior cohorts.METHODS: The ATLAS post-approval study was a multicenter, prospective, single-arm, open-label study of wide neck (neck ≥ 4mm or dome-to-neck ratio <2) intracranial aneurysms in the anterior and posterior circulations treated with the Neuroform Atlas Stent and approved coils. The primary effectiveness endpoint was complete occlusion (Raymond-Roy class 1) on angiography in the absence of retreatment or significant parent artery stenosis (>50%) through 3 years post-procedure. The primary safety endpoint was occurrence of major stroke, ipsilateral stroke, or neurological death through 3 years post-procedure. Independent adjudication of primary endpoint outcomes was completed by an Imaging Core Laboratory and Clinical Events Committee.RESULTS: A total of 146 anterior and 101 posterior cohort subjects from the pre-market study population were enrolled for continued follow-up. Subject demographics and aneurysm anatomy were representative of pivotal trial findings. For anterior subjects, the mean aneurysm size was 6.1±2.4 mm and the mean dome-to-neck ratio was 1.2±0.3 mm. In posterior subjects, the mean aneurysm size was 7±2.7 mm and the mean dome-to-neck ratio was 1.2±0.4 mm. At 3-year follow-up, the percent of target aneurysm progressive occlusion rated the same or better was 84.4% (95% CI, 67.2% -94.7%) of anterior subjects and 90.0% (95% CI, 73.5% -97.9%) of posterior subjects. A primary safety event was reported in 0.7% (1/146) of anterior and 1.0% (1/101) of posterior subjects, respectively, with no neurological deaths.CONCLUSIONS: The results of the ATLAS post-approval study demonstrate durable treatment effectiveness and favorable safety outcomes.