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Ablation of MYB-dependent leukaemia phenotype in MLL-driven AML correlates with increased expression of MAFB

ABSTRACT: The transcription factor MYB plays a pivotal role in haematopoietic homeostasis and its aberrant expression is involved in the genesis and maintenance of acute myeloid leukaemia (AML). Our previous work on CEBPA mutants has demonstrated that not all AML types display the same dependency on MYB expression, rather this depends on the nature of the driving mutations. However, whether this difference in MYB expression dependency is a general trend in AML still remains to be further elucidated. In this study, we investigate the importance of MYB in human leukaemia by performing siRNA-mediated knock-down in cell lines modelling AML driven by different genetic lesions. We show that the reduction in proliferation and the concomitant induction of myeloid commitment observed in MLL-driven leukaemia upon suppression of MYB expression is not seen in AML cells with a complex karyotype. By performing transcriptome analysis, we demonstrate that reduction of MYB in the cell line that responds to its manipulation leads to a strong activation of MAFB expression. Correlating with these observations, stratification of publicly available patient data reveals a reciprocal relationship between the expression of MYB and MAFB, highlighting a novel connection between those two factors in such AML.

ORGANISM(S): Homo sapiens

PROVIDER: GSE149556 | GEO | 2023/04/29

REPOSITORIES: GEO

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