Acute myeloid leukaemia (AML) is the most common form of leukaemia in adults. AML is characterised by the overproduction of immature white blood cells (WBC) that are unable to functionally combat infection. AML is caused by chromosomal translocations of the mixed lineage leukaemia (MLL) gene leading to the expression of aberrant MLL-fusion proteins blocking WBC maturation.

Recent studies have shown that the production of MLL can be prevented by the use of synthesised inhibitors that are able to specifically block bromodomain containing protein 4 (Brd4), which controls the recruitment of a transcriptional regulator complex known as the positive transcription elongation factor b (P-TEFb). The significance of this discovery has led to comprehensive studies of the Brd4-P-TEFb interaction as a therapeutic target for MLL-fusion leukaemia.

Importantly, the same inhibitors that target Brd4 also have efficacy against Brd3, a closely related bromodomain protein. Brd3 has also been identified to bind P-TEFb; however, comparatively little information exists regarding this interaction. This project aims to determine the molecular details of the Brd3-P-TEFb interaction. Protein constructs of Brd3 and Cyclin T1 (CycT1), one component of P-TEFb, have already been cloned, expressed and purified and potential interaction sites were tested in nuclear magnetic resonance (NMR) experiments to analyse the Brd3-P-TEFb complex. The other component of P-TEFb, known as cyclin-dependent kinase 9 (Cdk9), is yet to be tested for an interaction with Brd3 but is a future aim of this research.

Characterising the Brd3 and P-TEFb interaction is relevant in order to elucidate the role of Brd3 in the context of P-TEFb-mediated transcription, and to subsequently identify any off-target effects associated with inhibiting Brd3 function for the effective treatment of MLL-fusion leukaemia.