Why do some people with MDS develop AML?
Myelodysplastic Syndrome (MDS) is a malignant disease of the bone marrow stem cells (HSCs) that leads to an impaired ability to make normal numbers of healthy blood cells and a risk of transformation to acute myeloid leukaemia. The latter confers a very short life expectancy and treatment options are limited. We wish to understand the reasons why some MDS patients have a higher propensity to leukaemia transformation.
We will investigate whether there is a link between the phenomenon of a host immune system attacking its own cells (autoimmunity) and a protective mechanism against progression to leukaemia. We will examine the different protein expressions on the surface of HSCs in high and low risk MDS patients to see if any specific proteins are over-expressed. We will then test whether these proteins can trigger an autoimmune response in the hosts’ immune system. This could pave the way for future treatment approaches. Firstly, the over-expressed proteins on MDS cells could be the target for highly selective chemotherapy. Secondly, if some over-expressed proteins generate an autoimmune response then a vaccine-based therapy, using these proteins, could be developed to strengthen this autoimmune response, enabling the patient’s immune system to eradicate the cancer cells more effectively.