Prof Ken Mills                                                                                                    Dr Lisa Crawford

There are many different types of blood cells and, therefore, many types of blood cancers, each with different prognosis and unique treatments approaches. A wide team of researchers with diverse expertise is working at the PGJCCR, mirroring the multiple disease types and equally multiple challenges associated with the treatment of Blood Cancers.

Blood Cell Development and Blood Cancers. All the different types of blood cells develop from one type of cell called a stem cell. Blood cancers occur when a change in the DNA of a blood cells stop it from developing normally. The blood cells that are affected in different types of blood cancers are shown in the coloured boxes. (Figure credit: Prof Ken Mills)

DNA mutations are the main cause of blood cancers, and as such we are investigating how mutations alter normal blood cell development. Once we fully understand these molecular changes and what happens when they occur, we can use that knowledge to develop very targeted therapies. An important aspect of this work involves understanding how specific mutations affect both disease progression and DNA damage and repair (Katrina Lappin, Kienan Savage); but also what molecules are important in regulating DNA stability – how is held together (Adone Mohd-Sarip).  

Specifically in lymphoid diseases, one of our labs has developed a new way of detecting abnormalities to chromosomes and DNA mutations.  This method has the potential to improve the way that these diseases are diagnosed and monitored (Prof David Castro Gonzalez). In the case of Multiple Myeloma, mutations cause continuous production of antibodies and the malignant cells rely on specific molecular pathways to manage this excess: we are trying to understand how alterations in these protein handling pathways contribute to MM, as well as how these cells become resistant to drug treatments, to identify opportunities and alternative therapeutic interventions (Lisa Crawford, Rich Williams, Dessi Malinova).

Working with colleagues in the Belfast Health and Social Care Trust (Mark Catherwood), we are contributing data to ERIC, European Research Initiative on CLL, with a focus on the impact of a specific gene mutation in Chronic Lymphoid Leukaemia (CLL). Additionally, Dr Effie Kostareli, is studying the mode of action of an individual therapy for CLL to identify patients who will respond best to this drug.

Supported by Myeloma UK, the Department for the Economy (DfE) and Almac Ltd, Dr. Ian Overton's group are applying data-intensive computational analysis approaches to overcome resistance to therapy in Multiple Myeloma.

(…) the need to improve outcomes are causing a rapid evolution in the treatment of acute leukaemia, and it is encouraging to see advances in research. The availability of new technologies which allow researchers and clinicians to sequence the exact genetic changes occurring in the leukaemia cancer cells are now routine. This has provided a much more in depth understanding of what is causing the disease and is helping us understand which patients will benefit from which treatments. At the same time, new potent and targeted therapies directed at individual genetic changes are now emerging into routine clinical use.

Our academics and clinicians are working alongside European partners to resolve these challenges, and our research involves coordinating large amounts of information, such as a EU-wide Big Data project (HARMONY), to identify the way mutations interact and influence disease development.

We are also securing for the future of research in Blood Cancers: researchers at Queen’s are co-leading an international Masterclass for laboratory and clinical scientists on Next-generation sequencing for Blood cancers (Mark Catherwood, Jaine Blayney, Ken Mills), where they can receive training in techniques, technology and analyses for next generation sequencing data – we’re part of a health revolution! (NEMHESYS).

There are many drugs and therapies being used for many diseases such as diabetes, dementia or cardiac diseases, and we know these drugs are safe. So we are now investigating if some of them could be “repurposed” for blood cancers, specifically AML.  We are using a computational approach called MuSICAL to identify unexpected but effective combinations of approved drugs. An added benefit of this approach is reduced cost and time to identify novel drug combinations.  In a related project (My BLOCk), we have adapted the MuSICAL approach to use drugs that are current standard of care for AML - here we assess samples from patients at diagnosis and identify the best possible therapeutic combination for individual patients, making everyone’s treatment as personalised as possible.  Supported by Myeloma UK, the Department for the Economy (DfE) and Almac Ltd. Dr Ian Overton's group are applying data-intensive computational analysis approaches to overcome resistance to therapy in Multiple Myeloma,

Many drugs are originally derived from natural products, such as aspirin, and we have identified a specific agent from snake venom that has an anti-leukaemia effect for Acute Lymphoid Leukaemia (ALL). This is important because this agent enhances the effect of current therapies, and may allow using those at a lower, less toxic, dose (Ken Mills, Karen McCloskey)

“Scientific advances in treating blood cancers continue to be made on several frontiers. Research into new drug treatments can provide new cures, longer remissions, and less side effects. Completely new techniques also continue to be developed such as CAR-T therapy where important ‘T-cells’ in the patient’s own immune system are reprogrammed to fight off their cancer. At present this is most commonly used in advanced cases, but clinical trials continue to explore its potential, improve its effectiveness and expand its overall role in treatment".