Unlocking the genetic code of blood cancer

advancing genetic methods to improve patient care

Dr Allsup’s patients would come to his clinic with no obvious symptoms, or even no symptoms at all. In fact, the blood cancer was often discovered incidentally through routine health checks and blood tests – and patients were found to have this type of leukaemia.

He explained: “For a lot of people, this blood cancer just sits there and never changes and they live their whole life, and it's never caused any bother. But in other people, the blood cancer progresses, and they can become unwell and be susceptible to infections. Sadly people may ultimately die from the blood cancer.”

He was deeply intrigued by their stories and how other family members were also diagnosed with the disease. Dr Allsup became determined to unravel the genetic mystery behind why people get CLL, and why it can have such a varied presentation in different patients.

Dr Allsup, who is a Senior Lecturer in Haematology at Hull York Medical School, has had a longstanding research interest in CLL. He said, “In the last nearly 10 years, I've been pushing using advanced genetic methods to improve patient care. I have been trying to deliver that in my NHS practice, as well as contribute to pushing it forward in the research agenda.”

He got to work with collecting samples from patients with blood cancer. This work was heavily supported by the Daisy Tissue Bank, a biobank also located on the same hospital site near Dr Allsup’s clinical practice at Castle Hill Hospital, part of Hull University Teaching Hospitals NHS Trust in Hull. Armed with this large set of donations, they used this as a driver to collaborate with researchers at other institutions.

The genetic breakthrough

Early in the research, Dr Allsup formed a collaboration with Professor James Allan from Newcastle University. Professor Allan had a strong interest in constitutional genetics; where some people are predisposed to have certain diseases or have a disease that has a more aggressive course.

Over time, their research built to become a huge collaborative effort between several institutions: Hull York Medical School, Hull University Teaching Hospitals NHS Trust, Newcastle University, Cardiff University, Leeds University, Leicester University, Liverpool University, Oxford University, Southampton University, The Royals Marsden NHS Foundation Trust, and the Institute for Cancer Research in London.

Harnessing the combined knowledge from all these institutions, and equipped with their large shared dataset of CLL blood donations, the researchers pooled data from multiple studies.

Their findings were groundbreaking; they identified two specific genetic markers which they found would predict how the disease will progress in individual patients.

And in a further development, they found that that how the cancer progresses is influenced by both the genetic differences that a person is born with, and the genetic changes that occur in the cancer cells during the disease.

Dr Allsup said, "We found that we can pinpoint who is inherently more susceptible to have blood cancer that behaves in a more active and aggressive way."

Dr David Allsup said, “It opens the way to a personalised medicine approach. Our work is a step in that direction. It's not an endpoint, but it's the direction of trying to understand how someone's genetic makeup can influence susceptibility to cancer and how it how it progresses.”

Their discovery was published in the journal Nature Communications, one of the most highly cited multidisciplinary journals in the world. 

Professor Allan and Dr Allsup were keen to share their findings with those affected by CLL, and hosted a webinar to share their findings through CLL Support, a patient-led charity to support CLL patients and their families. Over 300 people affected by CLL attended their webinar.

Dr Allsup explained, “We’ve had very strong engagement from the local patient community. Whenever I discuss the CLL research with patients, they're always very supportive of work to further the understanding of why some patients have aggressive disease and others do not.