14 November 2024

KHP News sits down with Prof Eric So, Professor and Chair in Leukaemia Biology, King’s College London, to talk about his team’s work on the molecular biology of normal and leukaemia stem cells (LSCs). Understanding normal and LSCs will transform how patients react to treatment.

Please introduce yourself and tell us about your role

I was born and raised in Hong Kong, but have had a strong connection to the UK throughout my career. When I studied for my PhD at the University of Hong Kong, I spent a substantial amount of time in London at the Institute of Cancer Research (ICR), collaborating with Prof Sir Mel Greaves on a project that turned out to be extremely fruitful. It led me to finish my PhD in a record-breaking time of two-and-a-half years, winning the gold medal award for best PhD thesis of the year. So I have very fond memories of working in the UK. 

After my PhD, I did my postdoc with two world-leading experts in leukaemia research at Stanford University in America. While my wife and I really enjoyed our time in California, I was also able to make some important discoveries in leukaemia and stem cell biology. In 2004, I was brought back to London as part of a reverse brain-drain campaign to setup my research team at ICR with Mel. 

By combining and utilising what I had learned from experts in different continents, my group became one of the country’s leading laboratories studying leukaemia biology and potential treatments. In 2009, King’s College London joined forces with King’s College Hospital NHS Foundation Trust (FT) and offered my group a significant recruitment package with recurring research support that enabled us to develop new and important research areas. Therefore, I decided to leave ICR and bring 10 senior researchers with me to set up a leukaemia and stem cell biology lab here. 

Since then, our lab has excelled to become a world-leading authority in leukaemia biology and personalised therapy. This is a great example of the university and Trust working together to bring prestige and new discoveries to help patients. In addition, we have also trained many PhD students and postdocs from all over the world, to ensure the legacy continues. 

Please tell us about your research

Our lab is interested in understanding the molecular biology of normal and leukaemia stem cells with an aim to find better and more effective treatments for the patients. Stem cells are the most important cell type, which generate many different cells, tissues and organs in our body. In the blood system, haematopoietic stem cells (HSCs) produce all the white and red blood cells.

White blood cells are required to fight various infections and even cancer, while red blood cells transport essential oxygens to different parts of our body. Therefore, a lot of diseases associated with blood cell defects, ranging from bone marrow failure to leukaemia, can be cured in the clinic by transplanting a sufficient amount of normal HSCs to patients.  

Understanding the regulation of HSC function can help us to design effective strategies to amplify and manipulate these cells to achieve the best clinical outcomes for patients. On the other hand, we know that leukaemia cells originate from normal haematopoietic stem and progenitor cells (HSPCs) - carrying specific genetic mutations, such as mixed lineage leukaemia (MLL) gene rearrangement. 

Importantly, we know that not all cancer cells are created equally. Many cancer cells are short-lived, and leukaemia is sustained by a small number of what we call leukaemia stem cells (LSCs). Like normal HSCs, LSCs have unlimited self-renewal/generating ability and are resistant to standard chemotherapy. These cells are responsible for the cancer relapses that ultimately kill patients.

In order to cure these diseases, we need to understand the biology and develop effective therapeutics to target these LSCs while sparing the normal HSCs. This is another major area that we are actively studying.

What is the potential of the research and benefits to patients?

A prime example of our research and its potential to benefit patients is illustrated in our recent discovery, which was published in the Blood journal - the most prestigious and impactful journal in the field of haematology – and featured on the front cover. This study was conducted by my research fellow in King’s College London Jennifer Lynch, collaborating with my senior scientists Tsz Kan Fung and Bernd Zeisig from King’s College Hospital NHS FT.

In the study, we show that the survival and expansion of HSCs are regulated by the crosstalk between a group of proteins, call b-catenin/Hoxa9/Prmt1. B-catenin and Hoxa9 control the level of Prmt1 that is key to determine the integrity of HSC function. We demonstrate that a lack of Prmt1 function will lead to stem cell depletion, and conversely activation of Prmt1 can enhance HSC functions. 

If we can modulate the activity of these proteins to increase the functions of Prmt1, we will be able to improve the HSC functionality and make them more resilient and responsive to expansion upon bone marrow transplantation. Bone marrow transplant (BMT) is the most effective and long-lasting cure for an array of severe haematological disorders, including bone marrow failure and leukaemia.

However, it carries a significant number of risks, partly due to its incapability of having enough functional HSCs to rescue the blood system of the patients. Various molecules are being developed to modulate the activity of the proteins we identified, and their future application can have a significant benefit to these patients.

To achieve success in this study, we assembled an incredible team of researchers with complementary expertise, who were supported by the university and Trust. They worked together to reveal the molecular regulation of HSC function. This collaboration would not be possible without the support of the university and Trust. It is a testimony to KHP’s commitment to develop novel and more effective personalised health care for our patients. 

What led you to have a career in leukaemia and stem cell biology?

When I was a child, I always wanted to have a career that was dynamic and innovative. I knew I wanted to carry out research to not only learn but to make new discoveries, which could make a real difference and be passed on to future generations. 

My interest in leukaemia started when I was a PhD student studying infant/childhood leukaemia. I worked closely with my clinical colleagues and patients, and witnessed firsthand their desperation when faced with this aggressive and devastating disease. I wanted to do something to help and contribute in this area.  

Throughout my career I’ve been honoured and blessed to work with many honest and talented people around the world, making important discoveries to help improve patient care while doing the work I love.   

King’s Health Partners Haematology aspires to be a world-leading, patient-centred clinical academic partnership, taking the latest research from bench to bedside, supporting and training healthcare professionals to provide the best possible care for people with blood disorders. Find out more here.