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 has demonstrated that not all AML types display the same dependency on MYB expression and that MYB dependence is dictated by the nature of the driver mutation. However, whether this difference in MYB 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 line models of AML with different driver lesions. We show that the characteristic reduction in proliferation and the concomitant induction of myeloid differentiation that is observed in MLL-fusion-driven leukaemia upon MYB suppression is not seen in AML cells with a complex karyotype. By performing transcriptome analysis, we demonstrate that a strong activation of MAFB expression driven by MYB ablation is restricted to MYB-dependent cells. In line 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 AML.

中文翻译：

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MLL驱动的AML中MYB依赖性白血病表型的消融与MAFB表达增加有关。

转录因子MYB在造血稳态中起关键作用，其异常表达与急性髓细胞性白血病（AML）的发生和维持有关。我们以前的工作表明，并非所有AML类型都对MYB表达显示相同的依赖性，并且MYB依赖性由驱动程序突变的性质决定。但是，MYB依赖性的这种差异是否是AML的普遍趋势，仍有待进一步阐明。在这项研究中，我们通过在具有不同驱动器病变的AML细胞系模型中进行siRNA介导的敲除，来研究MYB在人类白血病中的重要性。我们表明，在具有复杂核型的AML细胞中未观察到在MLB融合引起的白血病MYB抑制后观察到的增殖特征降低和髓系分化的伴随诱导。通过执行转录组分析，我们证明了由MYB消融驱动的MAFB表达的强激活仅限于MYB依赖性细胞。与这些观察结果一致，对可公开获得的患者数据进行的分层揭示了MYB和MAFB表达之间的相互关系，突显了这两个因素在AML中的新颖联系。