Exposing the interdependent mechanisms of the leukaemic stem cell and the leukaemic niche in Chronic Myeloid Leukaemia

Dr Lisa Hopcroft, Institute of Cancer Sciences, University of Glasgow and John Goldman Fellow 2017

Chronic myeloid leukaemia (CML) is a blood cancer that arises from mutated stem cells in the bone marrow. There is evidence to suggest that, over time, the bone marrow becomes “pro-leukaemic”; that is, it changes to promote the survival of potentially cancerous mutated stem cells over non-mutated ‘normal’ stem cells. To eradicate these mutated stem cells and cure CML, we need to understand not only the cells themselves but also how the bone marrow protects them.

Dr Hopcroft’s team are comparing patterns of gene activity from three different groups of cells: mutated and non-mutated stem cells from Chronic Myeloid Leukaemia patients and normal stem cells from healthy donors. The team hope to achieve two aims with their research. 

Firstly, they hope to reveal how gene activity is controlled within the mutated stem cell. Dr Hopcroft and her team already know that three particular genes are important, but they want to work out exactly how they cooperate. To do this they are using computer-based methods using existing knowledge about which genes interact with each other to analyse the patterns of gene activity and work out to what extent these three genes show cooperative activity.

Secondly, by comparing non-mutated stem cells from CML patients and normal (non-mutated) stem cells from healthy donors, they are aiming to discover what effect the pro-leukaemic bone marrow environment has on stem cells in CML patients.

Understanding both of these aspects of CML will help to expose weaknesses of the disease that could be exploited by new therapies.