MYB as a Critical Transcription Factor and Potential Therapeutic Target in AML.

Myb was identified over four decades ago as the transforming component of acute leukemia viruses in chickens. Since then it has become increasingly apparent that dysregulated MYB activity characterizes many blood cancers, including acute myeloid leukemia, and that it represents the most "addictive" oncoprotein in many, if not all, such diseases. As a consequence of this tumor-specific dependency for MYB, it has become a major focus of efforts to develop specific antileukemia drugs.

MYB: A Key Transcription Factor in the Hematopoietic System Subject to Many Levels of Control.

MYB is a master regulator and pioneer factor highly expressed in hematopoietic progenitor cells (HPCs) where it contributes to the reprogramming processes operating during hematopoietic development. MYB plays a complex role being involved in several lineages of the hematopoietic system. At the molecular level, the MYB gene is subject to intricate regulation at many levels through several enhancer and promoter elements, through transcriptional elongation control, as well as post-transcriptional regulation.

MYB regulates the SUMO protease SENP1 and its novel interaction partner UXT, modulating MYB target genes and the SUMO landscape.

SUMOylation is a post-translational modification frequently found on nuclear proteins, including transcription factors (TFs) and coactivators. By controlling the activity of several TFs, SUMOylation may have far-reaching effects. MYB is an example of a developmental TF subjected to SUMO-mediated regulation, through both SUMO conjugation and SUMO binding.

MYB insufficiency disrupts proteostasis in hematopoietic stem cells, leading to age-related neoplasia.

MYB plays a key role in gene regulation throughout the hematopoietic hierarchy and is critical for the maintenance of normal hematopoietic stem cells (HSC). Acquired genetic dysregulation of MYB is involved in the etiology of a number of leukemias, although inherited noncoding variants of the MYB gene are a susceptibility factor for many hematological conditions, including myeloproliferative neoplasms (MPN). The mechanisms that connect variations in MYB levels to disease predisposition, especially concerning age dependency in disease initiation, are completely unknown.

Pioneer transcription factors are associated with the modulation of DNA methylation patterns across cancers.

Methylation of cytosines on DNA is a prominent modification associated with gene expression regulation. Aberrant DNA methylation patterns have recurrently been linked to dysregulation of the regulatory program in cancer cells. To shed light on the underlying molecular mechanism driving this process, we hypothesised that aberrant methylation patterns could be controlled by the binding of specific transcription factors (TFs) across cancer types.