Sub-Theme: Red Cells

Some people are born with anaemia inherited from their parents, while others develop anaemia later in their lives through other causes. Together these two forms of anaemia affect nearly a quarter of the world’s population, with profound effects on people’s health and the economy. Our centre brings together world leaders in anaemia research with the excellent clinical service provided in Oxford. Our research studies are looking at:

• Rare anaemia
• The role of iron metabolism in anaemia
• Anaemia and Myelodysplastic Syndrome (MDS)

Rare Anaemias

Our group is particularly interested in the genetics of red cell disorders. We use a range of genetic technologies to investigate the cause of the more commonly inherited anaemia, thalassaemia, and the rare inherited anaemias such as Congenital Dyserythropoietic Anaemia (CDA). In the long term, we hope that by combining state-of-the-art laboratory techniques with the Oxford clinical service, we will improve both diagnosis and treatments.

Our group also includes the national lead on studies of non-cancerous blood diseases, the NIHR Rare Diseases – Translational Research Collaboration website. (RD-TRC). The RD-TRC funds projects which investigate the physical characteristics and symptoms of rare genetic disorders. Current projects include work on inherited anaemias, Factor XI deficiency, inherited platelet disorders and paediatric (MDS) myelodysplastic syndromes.

Piecing the puzzle together: Congenital Dyserythropoietic Anaemia Type 1 (CDA-1)

CDA-1 is a very rare (one in a million) type of inherited anaemia. Patients range from requiring monthly blood transfusions to survive, to being tired and prone to absorbing excess iron from their diet. There is only one specific treatment for this condition, but not everyone responds to it and the side effects can be crippling. Only by understanding what goes wrong inside the cells can we come up with new treatments. In this photo is a red blood cell precursor from a patient with CDA-1- all of the little white holes should not be there. We have found some of the pieces of the puzzle to explain why that may be the case, but are missing some critical ones to complete the picture.

The Role of Iron Metabolism in Anaemia

Anaemia can also be caused by abnormalities in iron metabolism in the body. Our researchers are studying the molecular control of normal and abnormal iron metabolism, by focusing on the molecule hepcidin. In the last decade, hepcidin has emerged as the master regulatory hormone of iron metabolism. High levels of hepcidin inhibit iron absorption from the gut and inhibit the release of iron from storage cells, both of which decrease the amount of iron available for red blood cell production. This can contribute to anaemia and lead to a poor response to iron tablets. Our researchers are exploring whether measuring hepcidin levels in patients is a useful way to predict which patients will respond well to iron tablets. We would also like to find ways to decrease hepcidin levels, so that more iron is supplied to red blood cells, enabling a better recovery from anaemia.

Anaemia and Myelodysplastic Syndrome (MDS)

Professor Boultwood’s team investigates the molecular basis of MDS, a disorder affecting bone marrow cells. In patients with MDS, the production of all blood cell types is reduced, including red cells which leads to anaemia.

The team has previously shown that abnormalities in ribosomes (important protein factories in all cells) underlie the anaemia in the 5q-syndrome, a subtype of MDS. Prof. Boultwood and her team are currently studying what happens when drugs called translation enhancers (eg. L-leucine) and other drugs which have been shown to improve the anaemia in MDS (eg. ACE-536) with the aim to identify suitable MDS therapeutics.