Cookies on this website

We use cookies to ensure that we give you the best experience on our website. If you click 'Accept all cookies' we'll assume that you are happy to receive all cookies and you won't see this message again. If you click 'Reject all non-essential cookies' only necessary cookies providing core functionality such as security, network management, and accessibility will be enabled. Click 'Find out more' for information on how to change your cookie settings.

Acute Myeloid Leukemia (AML) develops due to the acquisition of mutations from multiple functional classes. Here, we demonstrate that activating mutations in the granulocyte colony stimulating factor receptor (CSF3R), cooperate with loss of function mutations in the transcription factor CEBPA to promote acute leukemia development. The interaction between these distinct classes of mutations occurs at the level of myeloid lineage enhancers where mutant CEBPA prevents activation of a subset of differentiation associated enhancers. To confirm this enhancer-dependent mechanism, we demonstrate that CEBPA mutations must occur as the initial event in AML initiation. This improved mechanistic understanding will facilitate therapeutic development targeting the intersection of oncogene cooperativity.

Original publication

DOI

10.1038/s41467-019-13364-2

Type

Journal article

Journal

Nat Commun

Publication Date

29/11/2019

Volume

10

Keywords

Animals, CCAAT-Enhancer-Binding Proteins, Cell Differentiation, Cell Lineage, Humans, K562 Cells, Leukemia, Myeloid, Acute, Loss of Function Mutation, Mice, Mutation, Receptors, Colony-Stimulating Factor