Transcription factor complexes in Acute Myeloid Leukaemia

Acute Myeloid Leukaemia (AML) is a group of blood cancers, resulting from uncontrolled cellular proliferation of cells belonging to the myeloid lineage. Lineage identity and differentiation is regulated by an interacting network of transcription factors. It is therefore not surprising that genomic alterations to the genes encoding components of transcription factor complexes (from single point mutations to translocations) are often implicated in the development of AML.

In this project we will investigate the role of the LMO2 complex and associated proteins in AML. The LMO2 complex is a haematopoietic transcriptional regulator involving a number of transcription factors and mediators. It is known to be required from the onset of haematopoietic development, but needs to be downregulated during differentiation. Recently we reported the interaction between PHF6 and the LMO2 complex. The aim of this project is to study the functional role of the interaction of PHF6 with the LMO2 complex and other transcription factors. We will use AML cell lines and patient samples and apply techniques such as tissue culture, Western blotting, mRNA expression analysis, quantitative PCR, CRISPR-Cas9 and shRNA knockdown, chromatin immunoprecipitation, immunohistochemistry by fluorescence microscopy, next generation sequencing. There will be the opportunity to learn genome wide data analysis.