Journal
LIFE SCIENCE ALLIANCE
Volume 2, Issue 2, Pages -Publisher
LIFE SCIENCE ALLIANCE LLC
DOI: 10.26508/lsa.201800207
Keywords
-
Categories
Funding
- Bloodwise Programme Grant [12010]
- College of Medical and Dental Sciences of the University of Birmingham
- European Research Council under the European Union's Horizon 2020 research and innovation programme [636855/StG]
- MRC [G0900892, G0701761, MC_UU_12009/7, MR/K01076X/1, MC_UU_00016/7] Funding Source: UKRI
Ask authors/readers for more resources
Mutations at the N- or C-terminus of C/EBP alpha are frequent in acute myeloid leukaemia (AML) with normal karyotype. Here, we investigate the role of the transcription factor Myb in AMLs driven by different combinations of CEBPA mutations. Using knockdown of Myb inmurine cell linesmodelling the spectrum of CEBPAmutations, we show that the effect of reduced Myb depends on the mutational statusof the twoCebpa alleles. Importantly, Myb knockdown fails to override the block in myeloid differentiation in cells with biallelic N-terminal C/EBP alpha mutations, demonstrating for the first time that the dependency on Myb is much lower in AML with this mutational profile. By comparing gene expression following Myb knockdown and chromatin immunoprecipitation sequencing data for the binding of C/EBP alpha isoforms, we provide evidence for a functional cooperation between C/EBP alpha and Myb in the maintenance of AML. This co-dependency breaks down when both alleles of CEBPA harbour N-terminal mutations, as a subset of C/EBP alpha-regulated genes only bind the short p30 C/EBP alpha isoform and, unlike other C/EBP alpha-regulated genes, do so without a requirement for Myb.
Authors
I am an author on this paper
Click your name to claim this paper and add it to your profile.
Reviews
Recommended
No Data Available