University of Birmingham
We currently have £19.4 million invested here, across 28 projects.
The University of Birmingham has been recognised for its world-class clinical research that’s driving better treatments for adults and children touched by blood cancers locally and across Britain.
In particular, Birmingham is one of the UK’s largest transplant centres. Stem cell transplants are often the last chance of cure for many patients of all ages with leukaemia, lymphoma and myeloma.
Unfortunately this vital treatment is still very risky, and can have some harmful side effects. Through our research we’re determined to make stem cell transplants available to all patients with blood cancers in the UK.
New ways to treat acute myeloid leukaemia
Stem cells in the bone marrow generate billions of different blood cells each day. This process involves many sequential steps which are each controlled by genes acting as regulators.
Leukaemia arises when the DNA of a stem cell is changed by genetic errors, which often occur in important regulator genes, disrupting the finely balanced sequence of blood cell production. The abnormal cells then develop into leukaemia cells that multiply and affect normal blood cell production.
Professors Constanze Bonifer and Peter Cockerill use state-of-the-art technology that analyses the activity of all genes within a cell. This is to identify the faulty molecules that switch hundreds of other genes on or off, causing acute myeloid leukaemia (AML). This will find new targets to hit with drugs to restore healthy blood cell production. But these faulty switches can also work differently in different patients, so these researchers are studying this to devise better tailored approaches to treatment.
Analysis of past clinical trial data suggests that patients who have higher numbers of circulating AML stem cells at the time of diagnosis have worse outcomes. Dr Sylvie Freeman is studying the impact of these cells in new trials in both older and younger AML patients. The aim is to understand the biology of the circulating cells and how to target them.
Professor Charlie Craddock is investigating the cells of AML patients who relapse after a stem cell transplant – a group that currently has little to no treatment options. His work will reveal how a new drug combination affects different parts of the patient's immune system and whether it affects different patients in different ways.
A clinical trial, run by Dr Ram Malladi at Birmingham, is testing a new drug in patients who have had a stem cell transplant for a blood cancer to see whether it can reduce serious complications that might otherwise prevent a cure.
Professor Mark Drayson and Dr Farhat Khanim at the University of Birmingham are looking at how the combination of a cholesterol-lowering drug and a female contraceptive pill can kill rogue cells in some blood cancers and whether other drugs can enhance the anti-cancer effect.
Developing and testing new drugs can be expensive and time consuming, but the use of existing drugs, especially in patients who cannot tolerate chemotherapy, is an intriguing approach to improving outcomes for patients.
Professor Paul Murray at the University of Birmingham will use his five-year programme to study how Hodgkin lymphoma (HL) and diffuse large B cell lymphoma (DLBCL) cells communicate with their surroundings to sustain survival and cell growth. Professor Murray has, up until now, focussed on HL, but the inclusion of DLBCL is a nice example of how research in one blood cancer can resourcefully translate into benefits for another.
New insight into chronic lymphocytic leukaemia
Professor Tanja Stankovic’s research focuses on drug resistance in chronic lymphocytic leukaemia (CLL), reflecting the fact that there are as yet no cures for this disease. Her team uses human cells and mice to test new ways to selectively kill certain types of drug-resistant CLL cells by exploiting weaknesses in their ability to properly repair DNA.
Professor Stankovic’s clinical fellow at Birmingham is working to identify faults that drug resistant CLL cells carry. These projects aim to discover how these signals can be disrupted to treat these diseases
Harnessing the immune system
As well as donating stem cells, transplants also transfer important cells of the immune system from the donor to the patient. In some cases the immune system of the donor attacks blood cancer cells in the patient, preventing relapse. This is called the graft versus leukaemia (GvL) effect and is extremely beneficial.
But not all patients have a strong GvL response. Professor Paul Moss at the University of Birmingham has long-term funding to investigate exactly how donor immune cells recognise and kill cancer cells. This will enable us to strengthen the GvL response for all patients in the future.
Professor Moss is supporting this research with an unusual clinical trial recruiting healthy volunteers who have offered to be stem cell donors. Research has shown that people with particular genetic make-up have an immune system that recognises blood cancer cells. Volunteers are given a harmless vaccine to stimulate their immune cells prior to the transplant, increasing the chances that the immune system will recognise blood cancer cells.
Improving care for children with leukaemia
The increase in the number of children who now survive the most common form of childhood leukaemia, acute lymphoblastic leukaemia (ALL) has been helped by the UKALL trials, which started in the 70s. These have guaranteed that breakthroughs in treatments and the same high standard of care is consistent for all children with ALL across the UK.
In April 2010, Bloodwise stepped in to manage the next stage of the trial, UKALL2011, which is being funded with help from Children With Cancer. Our researchers, and leading childhood leukaemia doctors, Professor Pam Kearns, at University of Birmingham and Dr Nick Goulden at Great Ormond Street Hospital, are managing this trial.