Identification of the genetic changes that cause cancers of the blood

01 March 2013
Dr Tom Vulliamy, Queen Mary University of London

The blood cancers myelodysplastic syndrome (MDS) and acute myeloid leukaemia (AML) arise spontaneously in most young patients, with unknown cause. However, there are some rare familial cases of MDS/AML in which more than one family member is affected. These family sets are a valuable resource for the identification of the genetic events that underpin these diseases. Dr Vulliamy is working with 26 such families to characterise these genetic mutations.

Amount of grant: £152,995  |  Date of award: March 2013


Myelodysplastic syndrome (MDS) and acute myeloid leukaemia (AML) are related cancers of the blood that together affect around 90 children a year in the UK.

Both diseases have a poor prognosis unless a stem cell transplant is possible.

The two diseases usually occur spontaneously with unknown cause. Previous work has shown that a number of different genes can be mutated in these patients, leading to disruption of normal blood development. In most patients, these mutations are acquired by the patient as part of the disease process. However, there are some rare examples of familial occurrence of MDS/AML, in which multiple members of the same family have the disease. These families have proved to be a valuable resource for the identification of the genetic events that initiate the disease process.

The research team is in contact with 26 such families, with more than one family member affected by MDS or AML. In ten of these families they have identified mutations in four different genes. The remaining 16 families remain genetically uncharacterised and are the subject of this project.

Developments in DNA sequencing technology now make it possible to identify the crucial genetic mutations that cause the disease in these families. The team will search for genes that are mutated recurrently in the affected families but only very rarely in the normal population.

They will follow-up on any such gene in two ways. Firstly they will look to see if the same gene is mutated in a larger group of sporadic MDS/AML patients. Secondly they will look into the functional consequences of the mutations in these genes.

About the research team

Dr Tom Vulliamy is a Senior Lecturer in Molecular Biology at the Blizard Institute’s Centre for Paediatrics. The main focus of his research is the identification of disease genes that cause bone marrow failure.

His is working with Professor Inderjeet Dokal, Chair of Child Health and Honorary Consultant in Haematology at Barts and the London School of Medicine and Dentistry.

The pair have an excellent track record in the genetic characterisation of blood disorders which has led to consistent publication record in high impact journals over a period of more than 15 years. What makes this team unique in its ability to carry out this work has been the recruitment of the rare families with these blood cancers, resulting from the years of activity and the reputation they have gained in this field of research.

What difference will this project make?

There is a significant need for new treatment approaches in MDS and AML as the responses to current therapy, beyond stem cell transplantation, are poor.

Not only will this work give an important insight to the underlying pathology of these two diseases, but improved classification should help to improve treatments.

There will be an important impact on the families that harbour the key genetic mutations. Knowledge of the underlying cause of an inherited disease can alleviate uncertainty and allow for pre-symptomatic and carrier testing.

Read more: About myeloid leukaemia

Where your money goes

Hover over a segment for details