| Title |
ASXL1 Mutations Promote Myeloid Transformation through Loss of PRC2-Mediated Gene Repression
|
|---|---|
| Published in |
Cancer Cell, August 2012
|
| DOI | 10.1016/j.ccr.2012.06.032 |
| Pubmed ID | |
| Authors |
Omar Abdel-Wahab, Mazhar Adli, Lindsay M. LaFave, Jie Gao, Todd Hricik, Alan H. Shih, Suveg Pandey, Jay P. Patel, Young Rock Chung, Richard Koche, Fabiana Perna, Xinyang Zhao, Jordan E. Taylor, Christopher Y. Park, Martin Carroll, Ari Melnick, Stephen D. Nimer, Jacob D. Jaffe, Iannis Aifantis, Bradley E. Bernstein, Ross L. Levine |
| Abstract |
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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X Demographics
Geographical breakdown
| Country | Count | As % |
|---|---|---|
| United States | 2 | 67% |
| Australia | 1 | 33% |
Demographic breakdown
| Type | Count | As % |
|---|---|---|
| Members of the public | 2 | 67% |
| Scientists | 1 | 33% |
Mendeley demographics
Geographical breakdown
| Country | Count | As % |
|---|---|---|
| United States | 4 | <1% |
| United Kingdom | 2 | <1% |
| Japan | 1 | <1% |
| Denmark | 1 | <1% |
| Germany | 1 | <1% |
| Canada | 1 | <1% |
| Belgium | 1 | <1% |
| Austria | 1 | <1% |
| Unknown | 494 | 98% |
Demographic breakdown
| Readers by professional status | Count | As % |
|---|---|---|
| Researcher | 104 | 21% |
| Student > Ph. D. Student | 95 | 19% |
| Student > Master | 40 | 8% |
| Student > Bachelor | 35 | 7% |
| Other | 29 | 6% |
| Other | 76 | 15% |
| Unknown | 127 | 25% |
| Readers by discipline | Count | As % |
|---|---|---|
| Agricultural and Biological Sciences | 133 | 26% |
| Biochemistry, Genetics and Molecular Biology | 117 | 23% |
| Medicine and Dentistry | 85 | 17% |
| Immunology and Microbiology | 8 | 2% |
| Chemistry | 5 | <1% |
| Other | 19 | 4% |
| Unknown | 139 | 27% |