MLL-AF9-induced leukemogenesis requires coexpression of the wild-type Mll allele.
Publication/Presentation Date
2-17-2010
Abstract
Oncogenic fusion proteins are capable of initiating tumorigenesis, but the role of their wild-type counterparts in this process is poorly understood. The mixed lineage leukemia (MLL) gene undergoes chromosomal translocations, resulting in the formation of oncogenic MLL fusion proteins (MLL-FPs). Here, we show that menin recruits both wild-type MLL and oncogenic MLL-AF9 fusion protein to the loci of HOX genes to activate their transcription. Wild-type MLL not only catalyzes histone methylation at key target genes but also controls distinct MLL-AF9-induced histone methylation. Notably, the wild-type Mll allele is required for MLL-AF9-induced leukemogenesis and maintenance of MLL-AF9-transformed cells. These findings suggest an essential cooperation between an oncogene and its wild-type counterpart in MLL-AF9-induced leukemogenesis.
Volume
17
Issue
2
First Page
148
Last Page
159
ISSN
1878-3686
Published In/Presented At
Thiel, A. T., Blessington, P., Zou, T., Feather, D., Wu, X., Yan, J., Zhang, H., Liu, Z., Ernst, P., Koretzky, G. A., & Hua, X. (2010). MLL-AF9-induced leukemogenesis requires coexpression of the wild-type Mll allele. Cancer cell, 17(2), 148–159. https://doi.org/10.1016/j.ccr.2009.12.034
Disciplines
Medicine and Health Sciences
PubMedID
20159607
Department(s)
Fellows and Residents
Document Type
Article