2010 - 2013
Dates of Study: Oct 2010 - Sept 2013
PhD Supervisor: Dr Brian Huntly
Studentship Sponsor: Wellcome Trust Research Training Fellowship
Thesis Title: The role of Sox4 in acute myeloid leukaemia
Following her PhD, Dr Putwain took up a position as a Veterinary Clinical Pathologist at PTDS Ltd. (Powell Torrance Diagnostic Services), UK.
Acute myeloid leukaemia (AML) represents a group of serious disease in which there is expansion of immature white blood cells. AML is heterogeneous with different subtypes of disease characterised by different abnormalities and mutations in the DNA, which translate to differing prognoses in patients. Maintenance of the bulk population of AML cells is thought to be dependent upon rare leukaemia stem cells (LSCs). It is likely that LSCs share many features with healthy haematopoietic stem cells (HSCs), which are responsible for forming all of the different cells in the blood. Improved understanding of the differences between HSCs and LSCs will help us to understand them better and design therapies to target the LSCs and treat leukaemia, whilst sparing the patient from toxic side effects. I examined the role of a particular gene Sox4, which is expressed in AML patients across different sub-types. I performed investigations to understand through which pathways the gene was acting and showed that this was in part through abnormal regulation of the cell-cycle. Using a drug to inhibit one of the targets of Sox4 I was able to reverse the leukaemia phenotype in cell models.
- Dawson et al., (2013). Recurrent mutations, including NPM1c, activate a BRD4-dependent core transcriptional program in Acute Myeloid Leukemia (2014). Leukemia