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Title of article :
ASXL1 Mutations Promote Myeloid Transformation through Loss of PRC2-Mediated Gene Repression
Author/Authors :
Abdel-Wahab، نويسنده , , Omar and Adli، نويسنده , , Mazhar and LaFave، نويسنده , , Lindsay M. and Gao، نويسنده , , Jie and Hricik، نويسنده , , Todd and Shih، نويسنده , , Alan H. and Pandey، نويسنده , , Suveg and Patel، نويسنده , , Jay P. and Chung، نويسنده , , Young Rock and Koche، نويسنده , , Richard and Perna، نويسنده , , Fabiana and Zhao، نويسنده , , Xinyang and Taylor، نويسنده , , Jordan E. and Park، نويسنده , , Christopher Y. and Carroll، نويسنده , , Martin and Melnick، نويسنده , , Ari and Nimer، نويسنده , , Stephen D. and Jaffe، نويسنده , , Jacob D. and Aifantis، نويسنده , , Iannis and Bernstein، نويسنده , , Bradley E. and Levine، نويسنده , , Ross L.، نويسنده ,
Issue Information :
روزنامه با شماره پیاپی سال 2012
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Abstract :
Summary ent somatic ASXL1 mutations occur in patients with myelodysplastic syndrome, myeloproliferative neoplasms, and acute myeloid leukemia, and are associated with adverse outcome. Despite the genetic and clinical data implicating ASXL1 mutations in myeloid malignancies, the mechanisms of transformation by ASXL1 mutations are not understood. Here, we identify that ASXL1 mutations result in loss of polycomb repressive complex 2 (PRC2)-mediated histone H3 lysine 27 (H3K27) tri-methylation. Through integration of microarray data with genome-wide histone modification ChIP-Seq data, we identify targets of ASXL1 repression, including the posterior HOXA cluster that is known to contribute to myeloid transformation. We demonstrate that ASXL1 associates with the PRC2, and that loss of ASXL1 in vivo collaborates with NRASG12D to promote myeloid leukemogenesis.
Journal title :
Cancer Cell
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