| Title | RUNX1 is a key target in t(4;11) leukemias that contributes to gene activation through an AF4-MLL complex interaction. |
| Publication Type | Journal Article |
| Year of Publication | 2013 |
| Authors | Wilkinson, Adam C., Ballabio Erica, Geng Huimin, North Phillip, Tapia Marta, Kerry Jon, Biswas Debabrata, Roeder Robert G., C Allis David, Melnick Ari, de Bruijn Marella F. T. R., and Milne Thomas A. |
| Journal | Cell Rep |
| Volume | 3 |
| Issue | 1 |
| Pagination | 116-27 |
| Date Published | 2013 Jan 31 |
| ISSN | 2211-1247 |
| Keywords | Amino Acid Sequence, Cell Line, Tumor, Cell Proliferation, Chromatin Immunoprecipitation, Chromosomes, Human, Pair 11, Chromosomes, Human, Pair 4, Core Binding Factor Alpha 2 Subunit, Gene Expression Regulation, Leukemic, Genetic Loci, Humans, Leukemia, Models, Biological, Molecular Sequence Data, Myeloid-Lymphoid Leukemia Protein, Oncogene Proteins, Fusion, Precursor B-Cell Lymphoblastic Leukemia-Lymphoma, Prognosis, Protein Binding, Protein Stability, Transcriptional Activation, Translocation, Genetic, Treatment Outcome |
| Abstract | <p>The Mixed Lineage Leukemia (MLL) protein is an important epigenetic regulator required for the maintenance of gene activation during development. MLL chromosomal translocations produce novel fusion proteins that cause aggressive leukemias in humans. Individual MLL fusion proteins have distinct leukemic phenotypes even when expressed in the same cell type, but how this distinction is delineated on a molecular level is poorly understood. Here, we highlight a unique molecular mechanism whereby the RUNX1 gene is directly activated by MLL-AF4 and the RUNX1 protein interacts with the product of the reciprocal AF4-MLL translocation. These results support a mechanism of transformation whereby two oncogenic fusion proteins cooperate by activating a target gene and then modulating the function of its downstream product.</p> |
| DOI | 10.1016/j.celrep.2012.12.016 |
| Alternate Journal | Cell Rep |
| PubMed ID | 23352661 |
| PubMed Central ID | PMC3607232 |
| Grant List | 090532/Z/09/Z / / Wellcome Trust / United Kingdom G0900747 91070 / / Medical Research Council / United Kingdom |