Clare Jonas
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A day in the life: Bela Wrench, acute lymphoblastic leukaemia researcher

Clare Jonas
Posted by
23 Jul 2018

Dr Bela Wrench tells us about how the cells around adult acute lymphoblastic leukaemia (ALL) cells might keep that cancer alive, how science and healthcare interact in her research, and playing golf.

Dr Bela Wrench
Dr Bela Wrench

How did you become a blood cancer researcher?

After training as a medical doctor, I decided that I would specialise in haematology, as I was particularly interested in linking diagnostic work (in the lab) with clinical care (in hospital settings). During my speciality training in haematology, I had the opportunity of working on national clinical trials in acute lymphoblastic leukaemia (ALL), looking at the potential role of a sensitive genetic test called minimal residual disease (MRD) to identify the patients who were most and least likely to relapse. We went on to show that MRD reliably picks out patients highly likely to relapse. This led to the MRD test becoming a routine tool for guiding treatment decisions in adult ALL. The work I did on MRD inspired me ask further questions about which cells and biological processes cause MRD, a theme I subsequently pursued with Bloodwise funding and into my current role as a Bloodwise Bennett fellow.

What are you working on now?

We know that many people who have adult ALL will not survive beyond a year from diagnosis. Even though most patients initially respond to chemotherapy, many relapse – only this time their ALL is treatment-resistant, and we cannot currently cure this resistant ALL.

Most blood cancer researchers now think that there is a ‘dormant’ (non-growing) group of ALL cells that is a major factor in relapse and treatment resistance. If we can better understand these dormant cells and work out how they remain in a switched “off” state then we may be able to reverse this process. This will force dormant cells into an active state and increase their responsiveness to treatment.

Interestingly, we have found that the environment of ALL cells (e.g. the other cells around them) plays a critical role in keeping ALL cells dormant. In particular, we think fat cells (adipocytes) in the bone marrow are involved in dormancy. Our theory is that that close contact with adipocytes causes ALL cells to become dormant. Therefore, disrupting the close interaction of adipocytes and ALL cells will be essential to preventing dormancy and making these cells responsive to treatment. Our ongoing mission is to find out about the proteins that allow ALL cells and adipocytes to be close neighbours, with the aim of identifying a treatment which stops them being so close.

We use a variety of methods including immunofluorescence, gene analysis, and examining samples through microscopes to obtain information that could help us work out ways to improve leukaemia treatments.

Immunofluorescence imaging demonstrating the close neighbourliness of ALL cells (green) with the adipocytes (red). Immunofluorescence works by ‘highlighting’ molecules so that they can be seen under a microscope.Immunofluorescence imaging demonstrating the close neighbourliness of ALL cells (green) with the adipocytes (red). Immunofluorescence works by ‘highlighting’ molecules so that they can be seen under a microscope.

Why do we need the research you do?

The successful treatment of children with ALL is a shining example of how successful integration of healthcare and laboratory science can dramatically improve outcomes. By applying the same integration in the setting of adult ALL, I aim to dramatically advance our understanding of the underlying biology of the disease. Specifically, our work highlights the importance of the environment surrounding ALL cells which nurtures them and prevents chemotherapy treatment from working fully. Understanding the ALL cell environment and how it supports ALL cells could help us to develop treatments that can sever this connection and improve treatment success.

What does your work mean for people who have blood cancer?

My work gives hope and reassurance that significant advances are being made in our understanding of how leukaemia cells are protected by their environment, allowing us to devise better approaches for achieving long-term cure for all patients.

What common misconceptions do people have about your job?

That I make breakthroughs every day! Whilst the cogs are continually turning, research is very much a journey where multiple experiments add up to the overall scientific outcome.

What's your favourite thing about your work?

Applying creativity and innovation to overcoming stubborn clinical challenges like treatment-resistant ALL. It’s also very enjoyable to achieve this goal through strong working relationships with highly dedicated teams across both scientific and clinical environments.

Members of Bela’s research team at work in the lab.

What's one of the hardest things about your work?

Inevitably, scientific research can throw up as many questions as it seeks to answer. Picking out many potentially important leads to follow can be challenging. I keep track of these leads on my ever-growing Pinterest pinboard for future research ideas.

 

What do you do when you’re not at work?

Exercise! Either through my 6 year old daughter’s energetic interactions or independently on the golf course! I also enjoy getting creative with cooking although I fall short of the expertise of my principal teacher, my mum, a masterchef in Gujarati Indian cooking.

If someone wanted to work in your research area, what advice would you give them?

If you have abundant curiosity and creativity plus a good dosing of tenacity, grit and determination, it’s the right work for you and can lead to an immensely rewarding experience – both in progressing scientific knowledge and knowing that you are making a real difference to the lives of people with blood cancer.

Is there anything you would like to say to Bloodwise supporters?

I’d like to offer immense and deepest thanks to all the hardworking supporters of Bloodwise for their continual support of adult ALL research. Your backing has been invaluable in developing studies which have allowed us to deeply examine dormancy, a fundamental problem in treating ALL. The work funded by Bloodwise has allowed us to gain significant insights into this issue and to identify an important factor within the microenvironment of ALL cells that promotes the dormancy behviour. With your ongoing support we aim to identify the specific communications between adipoctyes and ALL cells leading to dormancy. Armed with this knowledge we will be in a better position to develop effective approaches to overcome current limits to the effectiveness of treatment.

Dr Wrench is a Clinical Senior Lecturer at Barts Cancer Institute, Honorary Consultant at St Bartholomew’s Hospital, and the holder of a Bloodwise Bennett Fellowship – given to outstanding researchers who’ve recently finished their PhDs.

Innovative research like Bela’s can only happen thanks to support from you. Find out more about how you can help us continue our live-saving research, or about the ALL research we fund.

If you would like more information and support around ALL or any blood cancer, you can read our Online Patient Information, or speak to one of the Support Line Team on Freephone 0808 2080 888 (Monday-Friday 10am-4pm). You can also email support@bloodwise.org.uk.