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.
Journal article
2013-01-31T00:00:00+00:00
3
116 - 127
11
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