Before he left Cardiff University in 2014, Professor Alan Burnett had been chief investigator on the national trials in AML for over 20 years. Under his guidance the trials run by the Medical Research Council (later the National Cancer Research Institute) group became the largest in the world, and consistently explored novel therapies and trial designs. Under his auspices, a large bank of diagnostic AML samples was built up in Cardiff and at University College London; these are now under the management of a tissue bank coordinating group, led by Professor Nigel Russell as Chair of the AML Working Group, and Robert Hills of Cardiff University as statistician to the group.
"The Department of Haematology at Cardiff University has been actively engaged in the discovery of particular characteristics of blood cancer cells that can be targeted by new drugs. While we often know in some detail how genetic abnormalities occur in healthy blood cells, we really don’t understand how they contribute to the development of leukaemia.
Acute myeloid leukaemia research
My colleague Professor Darley and I at the Cardiff AML research group have for a number of years used model systems based on normal human blood stem cells to analyse the consequences of the development of common abnormalities found in leukaemia cells such as ‘AML1-ETO’, mutant ‘RAS’ or ‘FLT3’.
Some of our recent Leukaemia & Lymphoma Research funded studies have shown that a common feature in acute myeloid leukaemia (AML) is the over-production of molecules called reactive oxygen species (ROS), which can damage healthy DNA or alter the behaviour of genes. Current research is focused on understanding how ROS affects blood cells and how their inappropriate production can lead to leukaemia. What is exciting is whether current (and new) treatments might reverse the effects of ROS on blood cells.
The Cardiff AML team have also investigated another common abnormality in AML. Some leukaemia cells express a protein called CD200 which can help to suppress the patient’s immune system, protecting the leukaemia from attack. We recently showed in laboratory studies that we can block the effects of CD200 and restore the function of immune cells, which will go onto fight blood cancer. With the development of anti-CD200 drugs, the AML team are hopefully that we can test this new treatment in the near future.
Chronic lymphocytic leukaemia research
Similarly to the AML group, Cardiff has an internationally renowned team that focuses on chronic lymphocytic leukaemia (CLL). This group, led by Professor Chris Pepper (pictured above) recently developed a new model for investigating the behaviour of leukaemia cells under conditions that mimic what's happening in the bloodstream of patients. They are using this new model to uncover the mechanisms that enable leukaemia cells to escape the blood vessels.
These studies revealed that some patients' leukaemia cells have an increased ability to escape, making their disease more aggressive because the leukaemia only grows when the cells enter specialised tissues called lymph nodes. Importantly, the CLL team are using this knowledge to help us understand how new drugs like Ibrutinib and Idelalsib induce their clinical effects and to test rational combinations of old and new drugs that could be used to treat patients in the future.
Given the increased number of new drugs available for the treatment of CLL and AML, it's important that we develop ways of predicting the best treatment for individual patients. Not only do we need markers to predict response to drugs, we also need reliable markers of disease progression and clinical outcome.
In this regard, the CLL group recently published a large study showing that the length of specialised pieces of DNA found at the ends of chromosomes, called telomeres, can reliably predict CLL patient survival. With the support of Leukaemia & Lymphoma Research, the team are now working towards making this powerful test available to CLL patients. Cardiff also recently showed that we can now identify subsets of CLL patients who might particularly benefit from treatment with Ibrutinib and Idelalsib.
Chronic myelomonocytic leukaemia research
Cardiff University has also been actively engaged in the pre-clinical laboratory development of many new anti-cancer drugs. Tefinostat (CHR-2845) is one such agent which is targeted against blood cells called monocytes. Leukaemia & Lymphoma Research have recently agreed to fund a phase 2 clinical trial of Tefinostat, led by Dr Knapper, for patients with chronic myelomonocytic leukaemia (CMML), a rare form of blood and bone marrow cancer that currently has very few treatment options and a poor overall prognosis. The trial will be sponsored by Cardiff University and is expected to open in late 2015.
To test new agents for therapy, the University Hospital of Wales, Cardiff was awarded 'Trials Acceleration Programme (TAP) Centre' status in 2011 and has since been an active participant in TAP-sponsored early phase clinical trials for blood cancers including AML, CLL, myelodyplastic syndromes, myeloproliferative disorders and Hodgkin lymphoma. This has significantly increased the availability of such studies, and of new cancer therapies, to patients from South and West Wales. The TAP funding has paid for a full time clinical trials nurse, based in the Cardiff Clinical Research Facility; this grant has recently been extended for a further two years up to 2016."