Our Funded Research
Leukaemia
Developing better and safer medicines for children with leukaemia
With Professor Josef Vormoor
Many children with leukaemia can be cured, but the treatments still cause long-lasting and difficult side effects. Many researchers’ focus is on replacing these toxic treatments with new and safer options like targeted therapies.
Professor Josef Vormoor at Newcastle University is looking at combinations of new targeted therapies, which helps prevent cancer from becoming resistant to either medicine, to see which work well together and are most effective at fighting B-cell acute lymphoblastic leukaemia. His team have grown leukaemia cells from real patients so that they can test the combinations in a more realistic way. He hopes that these tests can provide evidence to run a clinical trial for any successful medicine combinations.
Project title: Screening for novel drug combinations in childhood B-cell acute lymphoblastic leukaemia
Lead investigator: Professor Josef Vormoor, Newcastle University
Funded by: The Little Princess Trust
Funded: November 2016
Award: £99,991.60
Developing a test to help treat leukaemia that has spread to the brain
With Dr Chris Halsey
Acute lymphoblastic leukaemia is the most common childhood cancer, and is a type of blood cancer. There have been excellent advancements in treatments and now most children can be successfully treated. However, it can be difficult to treat leukaemia that has spread to the brain. It is also difficult to test whether it has spread to the brain and there is no way to check whether the cancer will come back in the brain after treatment has finished.
Dr Chris Halsey and her team at the University of Glasgow will look at the tiny pieces of DNA and genetic material that leukaemia cells have shed to see whether they can be linked to leukaemia having spread to the brain. The researchers will also look at molecules present in samples to see whether doctors could use the presence of these molecules as an early warning that the cancer is returning. They hope to develop tests that will help children get the right treatments faster.
Project title: Developing leukaemic biomarkers to enable personalised CNS-directed therapy
Lead investigator: Dr Chris Halsey, University of Glasgow
Funded by: The Little Princess Trust
Funded: July 2017
Award: £99,993
Identifying combinations of repurposed drugs for new treatments of acute myeloid leukaemia
With Professor Ken Mills
Acute myeloid leukaemia is a serious form of leukaemia, the most common type of childhood cancer. The treatments for acute myeloid leukaemia are very difficult for children and have a lot of side effects. The goal for many researchers is to find new treatments that are effective at fighting the cancer whilst sparing children the difficult side effects.
Professor Ken Mills at Queens University Belfast is looking at whether existing medicines could be repurposed to treat acute myeloid leukaemia. His team will test different pairs of medicines to see whether two medicines are better than one, and if it stops the cancer from becoming resistant to either medicine. Ken hopes that by repurposing existing medicines, any good combinations of medicines could be used to help children with acute myeloid leukaemia much faster than a brand-new medicine could.
Project title: Facing the Music - identification of synergistic repurposed drug combinations as novel therapies in paediatric acute myeloid leukaemia
Lead investigator: Professor Ken Mills, Queen's University Belfast
Funded by: The Little Princess Trust
Funded: July 2018
Award: £98,712
Using existing medicines to target genetic errors
With Dr Kyle Matchett
Leukaemia is the most common type of childhood cancer, and acute myeloid leukaemia is a difficult to treat form of this cancer. There are also a lot of side effects for the treatments used, so new medicines are urgently needed.
Dr Kyle Matchett and his team at Ulster University are working on a gene called NRAS. Experts have found that, if it has errors, it is a common problem for children with acute myeloid leukaemia, and the researchers want to find a way to target this gene with existing medicines. Using existing medicines means that any found to fight NRAS errors can be used to help children sooner, as they have already been approved.
Project title: Targeting mutant NRAS in paediatric AML
Lead investigator: Dr Kyle Matchett, Ulster University
Funded by: The Little Princess Trust
Funded: January 2019
Award: £74,933
Investigating how DNA errors control leukaemia growth
With Dr Lisa Russell
Some children with leukaemia have errors in their DNA that lead to genes being turned on, allowing cells to grow far too fast. This can help cancer cells grow, but if the genes are turned on too often, it can kill the cancer cells. This means that cancer cells have to be careful not to switch the genes on too much.
Dr Lisa Russell at Newcastle University wants to identify all of the genes that the DNA errors are turning on and work on understanding how the errors and the genes interact. The researchers also hope to find medicines that could stop the DNA errors from turning the genes on to see if it could be a good treatment for childhood leukaemia.
Project title: RNA helicase DDX3X regulates JAK-STAT signalling in acute lymphoblastic leukaemia
Lead investigator: Dr Lisa Russell, Newcastle University
Funded by: The Little Princess Trust
Funded: January 2019
Award: £100,580
Stopping ‘cut-and-run’ DNA errors to help treat leukaemia and predict relapse
With Dr Joan Boyes
Your immune system makes millions of antibodies a day. There is a huge variety of antibodies, which recognise and fight specific infections, so different genes are mixed together to make the right one, like a patchwork quilt.
Dr Joan Boyes and her team at the University of Leeds have found a way that these pathwork antibodies are leading to acute lymphoblastic leukaemia. When the antibodies are made, it produces waste DNA that combines with an enzyme. This complex then cuts genes at random places, then runs away to cut somewhere else. The process is called ‘cut-and-run’. In this project, the researchers want to find out whether more of the ‘cut-and-run’ complex at diagnosis is linked to higher chances of the cancer coming back after treatment.
Project title: Towards inhibiting cut-and-run: An aberrant V(D)J recombination reaction that leads to lymphoid cancers.
Lead investigator: Dr Joan Boyes, University of Leeds
Funded by: The Little Princess Trust
Funded: August 2019
Award: £94,469
Understanding how some leukaemia cells survive treatment and cause a relapse
With Professor Julie Irving
Acute lymphoblastic leukaemia is the most common cancer in children. Most children can be cured, but sometimes the cancer comes back after treatment. When the cancer comes back after treatment, the DNA in the cancer cells is different than at the time the child was diagnosed. These ‘hardy’ leukaemia cells have taken over because they could resist chemotherapy.
Professor Julie Irving at Newcastle University is going to look at the DNA of the ‘hardy’ leukaemia cells to try and find markers that show whether a patient’s cancer could be treated by new medicines for relapsed and resistant cancers. The research team hope that this will show whether these new medicines could prevent relapse if given earlier.
Project title: Understanding and therapeutically exploiting clonal evolution in chemo-resistant acute lymphoblastic leukaemia
Lead investigator: Professor Julie Irving, Newcastle University
Funded by: The Little Princess Trust
Funded: August 2019
Award: £96,715.29
Fighting dormant leukaemia cells to stop relapse
With Dr Alexander Thompson
Leukaemia is a type of cancer that causes white blood cells, which are normally used to fight infections, to grow out of control. Current medicines fight leukaemia by attacking the common and fast growing leukaemia cells, but there are some slower growing leukaemia cells that can become dormant. These can then lead to the cancer coming back months or years later.
Dr Alexander Thompson at the University of Nottingham will be testing different medicines to see which can fight dormant leukaemia cells without harming healthy body cells. His team have found that dormant leukaemia cells use different resources to healthy cells. They will look into this further to find ways that medicines can target something that will hurt the leukaemia cell but not healthy cells.
Project title: Targeting refractory and dormant stem cells in childhood leukaemia
Lead investigator: Dr Alexander Thompson, University of Nottingham
Funded by: The Little Princess Trust
Funded: £238,793.41
Award: August 2019
Developing personalised treatments for childhood acute lymphoblastic leukaemia
With Dr Chris Halsey
Acute lymphoblastic leukaemia is the most common cancer in children. To cure it, doctors need to make sure that all of the leukaemia cells hiding around the brain are gone. They do this using chemotherapy, but it is difficult for doctors to know how much chemotherapy is needed as they do not know whether there are hidden cells and how many of them there are.
Dr Chris Halsey at the University of Glasgow is leading a study, part of an international clinical trial for leukaemia, that will use lasers to measure the amounts of leukaemia cells the are hidden in brain fluid samples. The research team hope to be able to identify children who don’t have many hidden cells and so could have less chemotherapy, meaning fewer side effects, and children who have lots of the hidden cells who might need different or stronger treatments.
Project title: ALLTogether1 CSF-FLOW Study
Lead investigator: Dr Chris Halsey, University of Glasgow
Funded by: The Little Princess Trust
Funded: December 2020
Award: £253,052
Could antibody errors lead to hard-to-treat leukaemias?
With Dr Joan Boyes
Our immune systems fight to keep our bodies healthy. They create millions of antibodies a day, with each antibody fighting a specific infection. Each of these antibodies is coded for in your DNA with a combination of genes.
Dr Joan Boyes at the University of Leeds has found a way that antibody production could leading to leukaemia. When antibodies are made, there is also a molecule created that can cut DNA, causing errors. After cutting DNA, the molecule moves on to cut elsewhere giving the process the name ‘cut-and-run’ errors. Her team will now be finding more out about whether this could be causing other types of leukaemia or playing a part in disease progression and relapse.
Project title: The Role of Cut-and-Run, an Aberrant V(D)J Recombination Reaction, in the Development of Acute Lymphoblastic Leukaemias with Poor Prognosis
Lead investigator: Dr Joan Boyes, University of Leeds
Funded by: The Little Princess Trust
Funded: December 2020
Award: £110,775.20
Testing albendazole as a safer treatment for childhood leukaemia
With Dr Kyle Matchett
Children treated for acute myeloid leukaemia can often struggle with serious side effects, and the treatments may not be very effective for some people.
Dr Kyle Matchett at Ulster University thinks that albendazole, an existing medicine already approved by the government, could treat a range of acute myeloid leukaemia types. The researchers plan to gather enough data to put this treatment into clinical trials. They believe that it could be used for patients a lot quicker than many new treatments because it has already been approved.
Project title: Investigating the preclinical efficacy of albendazole in paediatric acute myeloid leukaemia
Lead investigator: Dr Kyle Matchett, Ulster University
Funded by: The Little Princess Trust
Funded: December 2020
Award: £216,108
New ways to treat childhood acute lymphoblastic leukaemia
With Dr Anindita Roy
Most children with leukaemia can be successfully treated, but it is hard to treat children who develop leukaemia before their first birthday. These leukaemias are often linked to a gene called MLL, which we don’t know much about.
Dr Anindita Roy at the University of Oxford is creating a laboratory model of infant leukaemia by adding the MLL gene. Her team will use this model to understand how it becomes resistant, and to test medicines that could be used to treat infant leukaemia. These medicines will target the product of the MLL gene, a protein that helps the leukaemia resist treatment, which should kill the leukaemia cells.
Project title: Dissecting the role of CD133/PROM1 in MLL rearranged acute lymphoblastic leukaemia to develop novel targeted therapy
Lead investigator: Dr Anindita Roy, University of Oxford
Funded by: The Little Princess Trust
Funded: December 2020
Award: £219,194.66
How does T-cell acute lymphoblastic leukaemia go to the brain?
With Dr Chris Halsey
Acute lymphoblastic leukaemia is a common type of childhood blood cancer and has two subtypes: B-cell and T-cell. T-cell acute lymphoblastic leukaemia is rarer than B-cell acute lymphoblastic leukaemia and is harder to treat. If the cancer comes back after treatment, there often aren’t any more treatment options.
Dr Chris Halsey at the University of Glasgow is studying T-cell acute lymphoblastic leukaemia that has spread to the brain. Many children whose cancer has returned have leukaemia in their brains and there aren’t many effective treatments without serious side effects. The researchers will look at the genetic code of T-cell acute lymphoblastic leukaemia to find out which genes are vital to its survival. They will then test medicines that can block these genes to see if they could be a new treatment for relapsed leukaemia.
Project title: Identifying drivers of central nervous system involvement in T-cell acute lymphoblastic leukaemia
Lead investigator: Dr Chris Halsey, University of Glasgow
Funded by: The Little Princess Trust
Funded: December 2020
Award: £203,904
Using new technology to help children with blood cancers in low-income countries
With Dr Jonathan Bond
Most children with leukaemia in the UK and Ireland can now be cured, in part due to research into the genetic mutations in leukaemia cells. In low-income countries like Tanzania they have not been able to achieve the same results because of a lack of funding. However, scientific advances now mean that finding out what mutations a patient’s leukaemia has is relatively cheap. This means that doctors in low-income countries could start benefiting from the same knowledge that doctors have available in the UK.
Dr Jonathon Bond at University College Dublin is using new technologies to analyse the mutations in leukaemia cells from children in Tanzania. This is part of a collaboration with Children’s Health Ireland in Dublin, who have helped to support the treatment of Tanzanian children with cancer for over a decade. The research team plan to look at how the mutations in Tanzanian leukaemia cells causes the cancer to grow and resist treatment. This will help doctors predict which treatments would work best for each child and improve how children with leukaemia in Tanzania are treated.
Project title: Defining the molecular landscape of paediatric and adolescent acute leukaemia in Tanzania
Lead investigator: Dr Jonathan Bond, University College Dublin
Funded by: The Little Princess Trust
Funded: January 2021
Award: £78,303.03
ALL’ about metabolism: repurposing drugs for Acute Lymphoblastic Leukaemia
With Dr Nick Jones
T- cell acute lymphoblastic leukaemia is a type of childhood blood cancer where a part of your immune system called T-cells doesn’t develop properly. It can often become resistant to chemotherapy and is then difficult to treat.
Dr Nick Jones is looking at whether a diabetes medicine could be used to treat T-cell acute lymphoblastic leukaemia. They are called gliflozins and they can affect the way our cells use nutrients like glucose and proteins. This could interrupt the way that cancer cells change the way they use nutrients to grow faster. The team at Swansea University think that this could stop the leukaemia cells from becoming resistant to treatment.
Project title: Repurposing gliflozins for T-cell acute lymphoblastic leukaemia therapy
Lead investigator: Dr Nick Jones, Swansea University
Funded by: The Little Princess Trust
Funded: July 2021
Award: £280,532.67
Targeting nutrient use by childhood blood cancers
With Dr Francis Mussai
Cells need nutrients to survive, such as amino acids. Amino acids, and other nutrients, enter cells through special transporters. We know that removing a type of amino acid can starve cancer cells. This could be an alternative treatment for cancer, that has fewer side effects than chemotherapy.
Dr Francis Mussai and his team at the University of Birmingham are investigating what other nutrients acute myeloid leukaemia cells need. They plan to use a medicine to block the special transporters nutrients use to get into cells in the lab. They hope that this will starve the leukaemia cells and could be a future treatment for children with cancer.
Project title: Targeting LAT-1 dependent amino acid uptake as a novel therapeutic approach for paediatric AML
Lead investigator: Dr Francis Mussai, University of Birmingham
Funded by: The Little Princess Trust
Funded: July 2021
Award: £190,401.26
Improving bone marrow transplant for patients with high-risk leukaemia
With Dr Robert Wynn
On of the treatments for children with leukaemia is a bone marrow transplant. Blood cells are made in your bone marrow, so the donated bone marrow (either taken from a person, or from the blood in a donated umbilical cord) can produce healthy immune and blood cells instead of leukaemia cells. However, these new immune cells can attack the patient’s body because they see it as ‘foreign’. This can help cure leukaemia because those cells are seen as ‘foreign’ too, but it can also be very dangerous for children.
Dr Robert Wynn and his team at the University of Manchester believe that umbilical cord blood is better at fighting leukaemia and safer for the patient. As part of a trial where they boost the effects of cord blood transplants by giving patients additional immune cells, they want to find out how the cells made from cord blood transplants are different to those made from bone marrow transplants to understand how they work and whether transplants could work for other children’s cancers too.
Project title: Immune priming of donor-derived cord blood T-cells during allogeneic transplant of high risk and refractory leukaemia
Lead investigator: Dr Robert Wynn, University of Manchester
Funded by: The Little Princess Trust
Funded: July 2021
Award: £86,108
Safer treatments for children with acute lymphoblastic leukaemia
With Dr Tariq Enver
B-cell acute lymphoblastic leukaemia (B-ALL) is the most common cancer in children and children can be cured. However, high-risk B-ALL is very hard to treat and the treatments themselves can be very dangerous for children.
Dr Tariq Enver at University College London is working on a way to remove a gene that leukaemia cells are addicted to. His team’s experiments have shown that medicine blocking this gene starves leukaemia cells, even high-risk ones, without harming healthy cells. However, the medicine is very unstable so the team will be trying to create an improved version which could work in real life situations.
Project title: Developing Less Toxic Therapies For Children With Acute Lymphoblastic Leukaemia Through Targeting RUNX1 Addiction
Lead investigator: Dr Tariq Enver, University College London/Cancer Institute
Funded by: The Little Princess Trust
Funded: July 2021
Award: £168,381.38
Precision medicines for paediatric acute myeloid leukaemia
With Professor Julie Irving
Acute myeloid leukaemia is the second most common children’s leukaemia, but there are still not enough good treatment options. There has been a lot of progress in new medicines for adult cancers and researchers are keen to try to test these medicines in childhood acute myeloid leukaemia.
Around a third of children with acute myeloid leukaemia have errors in their genetic code which helps the cancer cells to grow, like some adults with cancer do. Professor Julie Irving and her team at Newcastle University are investigating which medicines (called ‘MEK inhibitors’) would work best for children, and whether they would work better in combination with other chemotherapy medicines. They hope this will help move this new treatment into a clinical trial, where it can help children with high-risk acute myeloid leukaemia.
Project title: Precision medicines for paediatric acute myeloid leukaemia
Lead investigator: Professor Julie Irving, Newcastle University
Funded by: The Little Princess Trust
Funded: March 2022
Award: £227,557
Using genetics to understand why acute myeloid leukaemia cells don’t respond to treatment
With Dr Karen Keeshan
Acute myeloid leukaemia is a difficult disease to treat. There can be problems because the treatment didn’t have enough of an effect, because the treatment was too toxic, or because the leukaemia came back after treatment. There aren’t that many treatments for children who have had problems with treatment, because researchers don’t know enough about the cells that cause the problems. These cells are called leukaemia stem cells and can stay in the body after treatment, leading to relapse.
The research team at the University of Glasgow, led by Dr Karen Keeshan, are looking at the genetic code of leukaemia stem cells to see what is making them not respond to treatment. They will look at the cells’ genes at diagnosis, after treatment, and when the patient relapses. They hope that this will show them the cells which don’t respond to treatment so that they can find specific medicines to fight those cells.
Project title: Using single cell transcriptomics to combat chemoresistance and disease relapse in paediatric acute myeloid leukaemia.
Lead investigator: Dr Karen Keeshan, University of Glasgow
Funded by: The Little Princess Trust
Funded: March 2022
Award: £132,500.00
Using medicines in new ways to treat acute lymphoblastic leukaemia
With Professor Christine Harrison
Your genetic code is stored in structures called chromosomes. These chromosomes have very specific structures and keep your DNA safe inside your cells. In cancer, there can often be changes to chromosomes like the structure being wrong, or having too many copies of a chromosome.
Professor Christine Harrison and her team at Newcastle University have found that there is a high-risk group of children with acute lymphoblastic leukaemia where there are lots of problems with chromosome number 21. They have also figured out which genes on the chromosome are likely to be causing the high-risk acute lymphoblastic leukaemia. In this project they will be assessing existing drugs to see which work to stop these genes’ effects. Dr Christine Harrison hopes to find drugs that are already licensed, so they can quickly start to be used to help children with cancer.
Project title: Novel drug treatments through repurposing of FDA-approved drugs for improved treatment of high-risk acute lymphoblastic leukaemia.
Lead investigator: Professor Christine Harrison, Newcastle University
Funded by: The Little Princess Trust
Funded: March 2022
Award: £188,962
Targeting proteins to fight acute myeloid leukaemia
With Dr William Grey
Treating acute myeloid leukaemia (AML) can be difficult, despite it being the second most common childhood leukaemia. The main reason that AML treatment fails is because there are still some of the original leukaemia cells left, which means that AML can come back.
The research team at the York Biomedical Research Institute, led by Dr William Grey, plan to study the proteins inside the original leukaemia cells to understand both how and why AML occurs. They hope that this will reveal new ways to target treatment at these original cells without harming a child’s healthy cells. They will also try to find out why AML develops from healthy tissue, to see if there is a way to prevent the disease.
Project title: Targeting protein homeostasis to eradicate leukaemic stem cells in paediatric leukaemia
Lead investigator: Dr William Grey, University of York
Funded by: The Little Princess Trust
Funded: March 2022
Award: £198,564.40
Stopping treatment resistance in T-cell acute lymphoblastic leukaemia
With Dr Frederik van Delft
Relapsed T-cell acute lymphoblastic leukaemia, which has come back during or after treatment, often can’t be treated with steroids as they no longer have an effect. Research has shown that using a medicine called Dasatinib alongside usual treatment can overcome steroid resistance for some patients. This is being considered as a treatment, but it is difficult and expensive to test whether it would work for a specific patient.
Dr Frederik van Delft and his team at Newcastle University plan to develop a new test which will measure the activity levels of a leukaemia cell process that is closely linked to whether Dasatinib works for that patient. They will also investigate the way that Dasatinib works to see if they can find more new treatments for steroid resistance.
Alongside this, the research team will analyse leukaemia cells, which Dr Frederik van Delft hopes will help them find other processes which are making the T-cell acute lymphoblastic leukaemia resistant to treatment
Project title: Kinase inhibition in the treatment of drug resistant T-cell Acute Lymphoblastic Leukaemia.
Lead investigator: Dr Frederik van Delft, Newcastle University
Funded by: The Little Princess Trust
Funded: July 2022
Award: £211,424
Blocking processes which keep leukaemia cells alive.
With Professor Owen Williams
Most children with this acute lymphoblastic leukaemia can be cured by chemotherapy, but this cancer still returns in a significant number of patients and is then very difficult to treat.
Professor Owen Williams and his team at University College London have discovered that acute lymphoblastic leukaemia relies on a process that takes place inside the cancer cells. When the process is blocked, it causes most acute lymphoblastic leukaemia cells to die – including those which returned after initial treatment.
In this project. Professor Owen Williams hopes to find out exactly how the cellular process is linked to the death of acute lymphoblastic leukaemia cells. The researchers also plan to use laboratory models of the cancer to find out whether this could create new treatment options.
Project title: Harnessing the STAT3/p53 axis for novel therapy of relapsed paediatric and TYA acute lymphoblastic leukaemia
Lead investigator: Professor Owen Williams, University College London
Funded by: The Little Princess Trust
Funded: July 2022
Award: £197,112.86
Understanding more about blood cancer in babies
With Professor Katrin Ottersbach
When babies are diagnosed with leukaemia, it is hard to treat and often comes back after treatment. The cancer starts before the child is born, which makes it hard to find out how it starts and why it progresses. Researchers don’t know what exact type of cell the cancer starts in, or why.
There are lots of different types of cells in your blood, which all have tiny molecules on their surfaces which show the exact type of cell and decide how the cell will behave. Professor Katrin Ottersbach at the University of Edinburgh believes that studying the different molecules and how the cells behave will help us to understand more about the start of infant leukaemia. In this project, she is focusing on one molecule and investigating how it changes the behaviour of leukaemia cells. The team’s next step will be to look at whether there are any chemicals which can stop this molecule, and whether this could lead to a new and better treatment.
Project title: Exploring the role of CSF1R as driver of lineage plasticity in MLL-r leukaemia
Lead investigator: Professor Katrin Ottersbach, University of Edinburgh
Funded by: The Little Princess Trust
Funded: March 2023
Award: £35,775.60
Finding out how leukaemia cells interact with babies’ immune systems
With Dr Samanta Mariani
Leukaemia in very young babies is very difficult to treat. It is different to leukaemia in other age groups, but there may be similarities that could help us understand more about why it starts and is so hard to treat.
In adults with leukaemia, a type of immune cell called macrophages can be hijacked by leukaemia cells to help promote the cancer’s growth. Researchers know that, in adults, killing the macrophages can make the cancer easier to treat with chemotherapy.
Dr Samanta Mariani at the University of Edinburgh wants to find out whether this also happens in babies with leukaemia. Her project aims to understand which immune cells are also present in infant leukaemia and what effect they have. If her team can find out more about how leukaemia cells interact with nearby immune cells, Dr Mariani hopes to find a way to change these interactions so that they no longer help the leukaemia grow and spread.
Project title: Immunotherapy for infant leukaemia: investigating and exploiting the leukaemia microenvironment to find new therapies to fight the disease
Lead investigator: Dr Samanta Mariani, The University of Edinburgh
Funded by: The Little Princess Trust
Funded: March 2023
Award: £140,214.54
Exploring new targeted therapy options for acute myeloid leukaemia in babies
With Dr Cristina Pina
Some rare subtypes of acute myeloid leukaemia , like MNX1 leukaemia, are only found in babies. There are very few cancer samples available for research, which makes it difficult to research better treatments. To get around this problem, Dr Cristina Pina’s lab at Brunel University London has created two different lab models for MNX1 leukaemia which can mimic the way patients’ cancer cells behave and respond to treatment.
In this project, the Dr Pina’s team will use their models to look for new treatments to fight MNX1 leukaemia. The team will be using existing medicines that are approved for use in other diseases, so any new treatment they find should be available for patients much faster than if it was a brand-new medicine. Wherever possible, the researchers will prioritise medicines known to be safe for children. By the end of the project, Dr Pina hopes to have selected 3-5 medicines to test further with the hopes of producing enough data to consider clinical trials.
Project title: Identification of therapeutic targets in MNX1-rearranged infant Acute Myeloid Leukaemia
Lead investigator: Dr Cristina Pina, Brunel University London
Funded by: The Little Princess Trust
Funded: July 2023
Award: £145,412.34
Investigating why some children get leukaemia after treatment for other cancers
With Dr Alex Thompson
Although childhood cancer treatments have improved in the last 10 years, some treatments can leave patients with long-term complications such as leukaemia later in life. This is very rare, very hard to treat, and doctors don’t fully understand how or why it happens. Researchers believe that treatments that damage cancer cell DNA could be linked to secondary leukaemia, if healthy cell DNA is also damaged.
We need to find out when and how DNA damage occurs that turns blood cells cancerous and allow them to ‘seed’ and grow alongside normal cells. In this project, Dr Alex Thompson at the University of Nottingham aims to compare the seeds that cause this type of leukaemia to equivalent healthy cells from the same patient. This will allow his team to find out what changes happen in the early stages of this type of leukaemia and look at which medicines which could target leukaemia ‘seeds’ without harming normal stem cells. .
Project title: Identifying and modelling the origin of therapy related childhood leukaemia
Lead investigator: Dr Alex Thompson, University of Nottingham
Funded by: The Little Princess Trust
Funded: July 2023
Award: £248,298.60
Could a medicine called ONC-201 help treat children with T-cell acute lymphoblastic leukaemia?
With Dr Nick Jones
T-cell acute lymphoblastic leukaemia (T-ALL) is a type of blood cancer in children, where some of their blood cells grow out of control. Some of the best medicines for T-ALL fight it by stopping the cancer cells from using nutrientsto grow. However, these medicines can also harm healthy cells.
Dr Nick Jones's project, at Swansea University, will look at whether a medicine called ONC-201 could be a better way to starve cancer cells. It works differently to the other medicines and doesn’t harm healthy cells. It is already in clinical trials for other cancer types, so it would be easier to introduce for children with leukaemia than a new medicine.
He will test how ONC-201 affects leukaemia cells and see how well it works on real leukaemia cells in the lab. If successful, this project could lead to a clinical trial testing ONC-201 as a safer treatment of childhood T-ALL.
Project title: Pharmacological targeting of the mitochondrial serine protease, ClpP for T-cell acute lymphoblastic leukaemia therapy.
Lead investigator: Dr Nick Jones, Swansea University.
Funded by: The Little Princess Trust.
Funded: February, 2024.
Award: £230,943.21
Designing a safer way to find and fight acute myeloid leukaemia cells in children
With Dr Karen Keeshan
Acute myeloid leukaemia (AML) is a type of blood cancer that is hard to treat in children. Researchers know that ‘leukaemia stem cells’ are the cells that start this cancer, and that make it grow back after treatment.
These cells are different to other cells and have special proteins and molecules on their surfaces. These molecules could be used to identify leukaemia stem cells. This means that they could also help treatments target these dangerous cells, and to track how the cancer is progressing.
Dr Karen Keeshan’s research team, at the University of Glasgow, has found a molecule called CD180 on acute myeloid leukaemia stem cells. In this project, she wants to find out more about it and see whether it could be used to find and kill AML cells.
The researchers will be looking at data from nearly 600 children with AML. They will look at whether all children with AML have CD180, and whether it is linked to how the cancer behaves. Dr Keeshan hopes to make a toolkit that can identify leukaemia stem cells and track the progression of AML.
Project title: Dissecting molecular profiles of childhood acute myeloid leukaemia for CD180 biomarker validation.
Lead investigator: Dr Karen Keeshan. University of Glasgow.
Funded by: The Little Princess Trust.
Funded: February 2024.
Award: £117,675.
Targeting a relapse-causing protein to treat childhood acute myeloid leukaemia
With Dr Rhys Morgan
Acute myeloid leukaemia (AML) is a type of blood cancer that is caused by errors in the genetic code. These genetic errors mean that cancer cells can make too many of certain proteins.
Many children with AML have too much of a protein called beta-catenin, which helps the cancer grow and survive treatment. Stopping the protein from working in cancer cells could help fight the leukaemia.
Dr Rhys Morgan’s lab at the University of Sussex found that beta-catenin interacts with RNA, a genetic molecule similar to DNA. Dr Morgan will look at how beta-catenin affects RNA in leukaemia cells, seeing if these interactions make AML worse.
The researchers will also look at how to stop these interactions with medicines. Dr Morgan hopes that his work will support the development of new targeted treatments to help children with AML. You can find out more about this project here.
Project title: Targeting beta:catenin:RNA/RBP interactions in paediatric acute myeloid leukaemia (pAML).
Lead investigator: Dr Rhys Morgan, University of Sussex.
Funded by: The Little Princess Trust.
Funded: July 2023.
Award: £249,968.78
Fighting circular DNA as a new way to prevent relapse in acute lymphoblastic leukaemia
with Dr Joan Boyes
DNA is the set of instructions that control how our cells behave. This means that it is very important to understand the DNA in cancer cells, which are cells that behave out of control.
In childhood acute lymphoblastic leukaemia (ALL), some cancer cells contain small DNA circles that scientists think are making the cancer worse by damaging other DNA. For example, having more DNA circles at diagnosis is linked to the cancer coming back after treatment (relapse). The circles copy themselves more in patients who relapse, meaning they cause even more damage to DNA.
In this project, Dr Boyes will test whether stopping the DNA circles from copying themselves could prevent relapse. Her team will look at whether drugs that work against a key gene pathway can affect the amount of new DNA circles made. These drugs are also used in other conditions, meaning that a treatment could be developed quickly if proven effective.
Project title: Inhibiting replication of circular DNA: A new way to suppress relapse of childhood acute lymphoblastic leukaemia?
Lead investigator: Dr Joan Boyes, University of Leeds.
Funded by: The Little Princess Trust.
Funded: July 2024.
Award: £61,556.33
