RUNX1 is a key target in t(4;11) leukemias that contributes to gene activation through an AF4-MLL complex interaction.

Journal article

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.

Authors: Wilkinson, A; Ballabio, E; Geng, H; North, P; Tapia, M

• Publication status: Published
• Journal: Cell reports
• Volume: 3
• Issue: 1
• Pages: 116-127
• Publication date: 2013-01-01
• DOI: 10.1016/j.celrep.2012.12.016
• EISSN: 2211-1247
• ISSN: 2211-1247
• Language: English
• Keywords: Amino Acid Sequence; Genetic Loci; Core Binding Factor Alpha 2 Subunit; Protein Binding; Cell Proliferation; Translocation, Genetic; Models, Biological; Prognosis; Humans; Oncogene Proteins, Fusion; Leukemia; Transcriptional Activation; Myeloid-Lymphoid Leukemia Protein; Molecular Sequence Data; Chromatin Immunoprecipitation; Treatment Outcome; Precursor B-Cell Lymphoblastic Leukemia-Lymphoma; Gene Expression Regulation, Leukemic; Chromosomes, Human, Pair 4; Cell Line, Tumor; Chromosomes, Human, Pair 11; Protein Stability