Acute myeloid leukaemia (AML)

Acute myeloid leukaemia (AML)

Leukaemia is a type of blood cancer that usually affects white blood cells and bone marrow. White blood cells are an important part of your immune system that fight infection, and bone marrow is where blood cells like these are made.

There are many different types of leukaemia. Some types develop faster, and are known as acute leukaemia. These include acute lymphoblastic leukaemia (ALL), acute myeloid leukaemia (AML), acute premyelocytic leukaemia (APL), and B or T-cell acute lympoblastic leukaemia.

But each type of leukaemia acts differently, and will need to be treated differently.

Around 2,420 people are diagnosed with acute myeloid leukaemia (AML) every year. 

AML affects cells involved in the production of a family of blood cell called myeloid cells, which include red blood cells, platelets and certain types of white blood cells. 

We don’t have a lot of treatment options for AML, and it can be hard to treat, especially in older people who have a higher risk of developing the disease. Standard treatment is chemotherapy, and stem cell transplant is usually considered if chemotherapy fails or people relapse after initially responding to treatment. 

Because there are limited avenues of treatment, and at the moment we don’t have any targeted therapies for AML, this is a type of blood cancer where our research investment is high.

Our portfolio of research spans from finding where the roots of AML lie - so we can combat the disease right from the beginning - to testing new treatments for people living with AML. 

 

Clinical trials for people living AML

We are supporting a number of clinical trials for people living with AML. Research is taking place to test new drug combinations as quickly as possible to find potential new treatments for older people with AML.

Doctors are also looking at ways of making stem cell transplantation more effective for people, and to prevent AML from returning after this procedure.

FIGARO trial

Chief investigator - Professor Charles Craddock, University Hospital Birmingham
Acute myeloid leukaemia (AML) Myelodysplastic syndromes (MDS)
A randomised trial of the FLAMSA-BU conditioning regimen in patients with acute myeloid leukaemia and myelodysplasia undergoing allogeneic stem cell transplantation
This trial is looking at a reduced intensity conditioning regimen called FLAMSA-BU. Researchers think that this treatment could improve outcomes in older people because of reduced side effects and a lower risk of AML or MDS returning. FLAMSA-BU will be compared with standard intensity conditioning.

ROMAZA trial

Chief investigator - Professor Charles Craddock, University Hospital Birmingham
Acute myeloid leukaemia (AML)
Phase I trial of romidepsin plus azacitidine in patients with newly diagnosed, relapsed or refractory acute myeloid leukaemia ineligible for conventional chemotherapy
People with AML are usually given chemotherapy, but not everyone can have this type of treatment. Researchers think that combining azacitidine with romidepsin may help people with AML who can’t have standard chemotherapy treatment.

VIOLA trial

Chief investigator - Professor Charles Craddock, University Hospital Birmingham
Acute myeloid leukaemia (AML) Myelodysplastic syndromes (MDS)
A phase I trial of combined azacitidine and lenalidomide salvage therapy in patients with acute myeloid leukaemia who relapse after allogeneic stem cell transplantation
People with AML or MDS are usually treated with high doses of chemotherapy, followed by a stem cell transplant. But AML and MDS can come back after a transplant, and when it does it becomes much more difficult to treat. Researchers want to know if combining azacitidine and lenalidomide can help this group of people.

RAvVA trial

Chief investigator - Professor Charles Craddock, University Hospital Birmingham
Acute myeloid leukaemia (AML) Myelodysplastic syndromes (MDS)
A randomised phase II trial of 5-azacitidine versus 5-azacitidine in combination with vorinostat in patients with relapsed acute myeloid leukaemia ineligible for salvage chemotherapy
In this trial, researchers want to know if azacitidine given with vorinostat is better than azacitidine alone in people with AML or high risk MDS who are unable to tolerate intensive chemotherapy.

Finding out why people with AML relapse

Some people with AML can be cured with intensive chemotherapy, but others will unfortunately relapse. We still don’t fully understand why this is, and want to know the reasons for the variation in treatment response.

It is now clear that AML is particularly complex, with each leukaemia composed of different populations of cells that can vary widely in their genetic make-up. Research indicates that it is this remarkable variation of AML that influences how people with AML respond to treatment, and could be responsible for relapse.

One way to improve treatment for AML is to develop tests that can identify people with AML who are at risk of relapsing, so their treatment can be tailored accordingly.

 

Pinpointing people who are at risk of relapsing

Lead researcher - Dr Richard Dillon, King’s College London
Leukaemia Acute myeloid leukaemia (AML)
Understanding heterogeneity of treatment response in “standard risk” acute myeloid leukaemia
Using a test that picks up the mutation in the NPM1 gene, Dr Dillon wants to detect cells in the bone marrow that might be able to lie dormant and resist chemotherapy, causing relapse. This test was developed with Bloodwise funding, and is already helping doctors guide treatment for people with AML. This research will tell us more about the cells that harbour the NPM1 gene change.

Immunotherapy for AML

Immunotherapy is a type of treatment that uses the power of the body’s immune system to fight a disease.

There are numerous immunotherapies already being used to treat blood cancer, and many others that are being developed and tested in clinical trials.

These include:

  • Chimeric antigen receptor (CAR) and T cell receptor (TCR) therapy
  • Donor lymphocyte infusion (DLI)
  • Monoclonal antibody therapy
  • Reduced-intensity allogeneic stem cell transplantation

Part of our research is using a treatment approach called T cell receptor (TCR) therapy, which harnesses the body's immune system to fight cancer cells.

Cancer can only develop because faulty cells are able to hide from a person’s immune system. Scientists are using TCR therapy to re-educate a patient’s own immune cells to kill the cancer. To do this, a person’s immune cells - T-cells - are taken from their body and reprogrammed in a lab to recognise particular proteins on the surface of the cancer cells. The immune cells are then given back to the patient, so that the cells will kill the cancer cells.

A major advantage of this type of cell therapy over existing treatment options is that immune cells can recognise specific markers on cancer cells, providing a basis for the selective attack of cancer while avoiding damage to normal tissues.

We are also supporting a trial that is looking at a new monoclonal antibody that specifically targets a protein on AML cells. Early studies have shown the drug works well in a lab, so now researchers want to see if it can help people with AML who have not responded to the usual treatments, or have AML that has come back after treatment.

Preventing relapse after chemotherapy or stem cell transplants is really important because AML can be harder to treat in these circumstances. Our research is looking at using immunotherapy to boost the killing ability of the immune system so it can fight back against leukaemia, and we also want to know if using an immunotherapy can help to make stem cell transplants more effective.

 

Fine tuning immune cells to be effective killers

Lead researcher - Professors Hans Stauss and Emma Morris, University College London
Leukaemia Acute myeloid leukaemia (AML)
Editing specificity and function to enhance T cell therapy of haematological malignancies
In blood cancer, the patient’s own immune system is generally impaired so is unable to attack cancer cells. Professors Stauss and Morris are using TCR gene therapy to develop treatments to boost the immune response against blood cancers.

Breaking down the defences of leukaemia

Lead researcher - Dr Cristina Lo Celso, Imperial College London
Leukaemia Acute myeloid leukaemia (AML)
In vivo analysis of the interactions between acute myeloid leukaemia, T cells and haematopoietic stem cells to inform the design of immunotherapy protocols
Using powerful microscopy, Dr Lo Celso and her team are analysing the evolving interactions between AML cells and T cells as disease develops. By understanding how AML cells switch off the immune system, researchers hope to target these mechanisms to help the immune cells to win against leukaemia.

Optimisation of the graft versus leukaemia effect to improve the outcome of haematopoietic stem cell transplantation

Lead researcher - Professor Paul Moss, University of Birmingham
Optimisation of the graft versus leukaemia effect to improve the outcome of haematopoietic stem cell transplantation
Researchers led by Professor Moss want to investigate exactly how donor immune cells recognise and kill cancer cells. The aim of this research is to find new ways to increase the strength of GvL so that transplant treatments can be modified to the needs of individual people.

PRO-DLI

Chief investigator - Dr Victoria Potter, Kings College Hospital, London
Acute myeloid leukaemia (AML) Myelodysplastic syndromes (MDS) Childhood Hodgkin Lymphoma
A phase II prospective trial of prophylactic donor lymphocyte infusions for the prevention of relapse post HSCT in patients with high risk myeloid malignancy
Stem cell transplantation may cure acute myeloid leukaemia (AML) and myelodysplastic syndrome (MDS), but unfortunately people can suffer a relapse after transplant. Researchers want to see if giving white blood cells from the stem cell transplant donor can be used after transplantation to prevent relapse.

Searching for new treatments for people with AML

Acute myeloid leukaemia (AML) is the most common aggressive blood cancer. It can be hard to treat, especially in patients over 65 years of age, and is often fatal within a year of diagnosis.

We still don’t have a lot of treatment options for AML. Standard therapy is chemotherapy, and stem cell transplant is usually considered if chemotherapy fails or people relapse.

Our research is looking for innovative ways to treat AML using targeted therapies, and to match existing therapies to the individual person so treatment has more success.

Discovering new leukaemia drugs

Lead researcher - Professor Terence Rabbitts, University of Oxford
Leukaemia Acute myeloid leukaemia (AML)
Targeting protein-protein interactions in leukaemia for novel therapeutics
Professor Terence Rabbitts and his team are looking at three different leukaemia proteins called LMO2, RAS and MLL, which interact with each other to cause leukaemia. The team want to develop small antibody fragments that can block specific protein interactions, which could in the future lead to a new treatment option for people with AML. 

Developing smarter and kinder treatments for AML

Lead researcher - Professor Eric So, Kings College London
Leukaemia Acute myeloid leukaemia (AML)
Functional dissection of transcriptional and epigenetic machinery in human leukaemia
Abnormal gene expression is a common feature in leukaemia, and emerging evidence shows that proteins called histone modification enzymes play a key role in this process. Professor So aims to define the role of individual histone modification enzymes in the development and treatment of leukaemia, particularly AML. This could lead to the development of more effective but less toxic leukaemia therapies.

Understanding what drives AML

Our researchers want to understand what makes a healthy blood cell become a leukaemic cell, so that we can develop improved treatments. We know that damage to the genetic code carried by all blood cells is important. However, we don't fully understand what these changes do to healthy cells, and how changes in different genes work together to cause leukaemia.

And whilst most research focuses directly on understanding and treating blood cancer, there is a huge amount to learn from studying how healthy blood cells develop. If we can understand what should happen normally, scientists can really get a grip on what is going wrong in blood cancer.

One area we are particularly interested in is blood stem cells. These are a tiny population of self-maintaining cells that give rise to the billions of new blood cells that are produced daily. Many leukaemias are known to be sustained by transformed blood stem cells – sometimes known as ‘leukaemic stem cells’ or “cancer stem cells” - as a result of genetic changes they have acquired that permanently disrupt their normal behaviour. If we can learn about the mechanisms that turn healthy blood stem cells into leukaemic cells, we may be able to reverse this process. 

Our research is looking at blood stem cells in great detail, and how their development goes awry in leukaemia. We are also looking at where we can target these processes, which could lead to much needed treatments for AML.

Targeting the genes that cause AML

Lead researcher - Dr David Wiseman, University of Manchester
Leukaemia Acute myeloid leukaemia (AML)
An investigation of the clonal and functional collaboration between IDH and SRSF2 mutations in acute myeloid leukaemia
One in five AML patients has a mutation in genes called isocitrate dehydrogenase 1 (IDH1) or IDH2. People with IDH gene changes also have mutations in another gene called SRSF2. The team aim to understand how these mutations work together to cause AML. They will also profile and evaluate new candidate drugs which target the mutated form of IDH1 to see whether these successfully kill leukaemia cells, potentially leading on to clinical trials.

What turns healthy blood stem cells into leukaemic stem cells?

Lead researcher - Professors Constanze Bonifer and Peter Cockerill, University of Birmingham
Leukaemia Acute myeloid leukaemia (AML)
Mechanistic insights into aberrant transcriptional programming in acute myeloid leukaemia
Professors Bonifer and Cockerill are investigating the complex processes that turn healthy cells into leukaemic cells. By understanding the causes of this transformation, they hope to find ways to prevent the development of AML - and to restore healthy blood cell production.

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