TY - JOUR T1 - Dependence on Myb expression is attenuated in myeloid leukaemia with N-terminal CEBPA mutations JF - Life Science Alliance JO - Life Sci. Alliance DO - 10.26508/lsa.201800207 VL - 2 IS - 2 SP - e201800207 AU - Giacomo Volpe AU - Pierre Cauchy AU - David S Walton AU - Carl Ward AU - Daniel Blakemore AU - Rachael Bayley AU - Mary L Clarke AU - Luisa Schmidt AU - Claus Nerlov AU - Paloma Garcia AU - Stéphanie Dumon AU - Florian Grebien AU - Jon Frampton Y1 - 2019/04/01 UR - https://www.life-science-alliance.org/content/2/2/e201800207.abstract N2 - Mutations at the N- or C-terminus of C/EBPα 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 in murine cell lines modelling the spectrum of CEBPA mutations, we show that the effect of reduced Myb depends on the mutational status of the two Cebpa alleles. Importantly, Myb knockdown fails to override the block in myeloid differentiation in cells with biallelic N-terminal C/EBPα 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/EBPα isoforms, we provide evidence for a functional cooperation between C/EBPα 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/EBPα-regulated genes only bind the short p30 C/EBPα isoform and, unlike other C/EBPα-regulated genes, do so without a requirement for Myb. ER -