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DOI: 10.1016/j.ccr.2012.06.032
¤ OpenAccess: Hybrid
This work has “Hybrid” OA status. This means it is free under an open license in a toll-access journal.

ASXL1 Mutations Promote Myeloid Transformation through Loss of PRC2-Mediated Gene Repression

Omar Abdel-Wahab,Mazhar Adli,Lindsay M. LaFave,Jie Gao,Todd Hricik,Alan H. Shih,Suveg Pandey,Jay P. Patel,Young Rock Chung,Richard P. Koche,Fabiana Perna,Xinyang Zhao,Jordan E. Taylor,Christopher Y. Park,Martin Carroll,Ari Melnick,Stephen D. Nimer,Jacob D. Jaffe,Iannis Aifantis,B Bernstein,Ross L. Levine

PRC2
Biology
Myeloid
2012
Recurrent 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.
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    ASXL1 Mutations Promote Myeloid Transformation through Loss of PRC2-Mediated Gene Repression” is a paper by Omar Abdel-Wahab Mazhar Adli Lindsay M. LaFave Jie Gao Todd Hricik Alan H. Shih Suveg Pandey Jay P. Patel Young Rock Chung Richard P. Koche Fabiana Perna Xinyang Zhao Jordan E. Taylor Christopher Y. Park Martin Carroll Ari Melnick Stephen D. Nimer Jacob D. Jaffe Iannis Aifantis B Bernstein Ross L. Levine published in 2012. It has an Open Access status of “hybrid”. You can read and download a PDF Full Text of this paper here.