Research

Why is research necessary?

There are two main types of  acute leukaemia. The most frequently occurring, Acute Lymphoblastic Leukaemia (ALL) is largely curable. However the less common form, Acute Myeloid Leukaemia (AML) has several sub types and has a much lower survival rate.

Acute Myeloid Leukaemia is currently treated with chemotherapy based around 3 main drugs (Cytarabine, Doxorubicin, and Etoposide). Some patients will respond to front-line chemotherapy and be cured. However for some children even if they respond initially, resistant cells can cause the AML to return and the child may eventually succumb and die of disease.

Despite multinational research over the last 20 years, no new drugs have been developed that have become clinically widely used for the treatment of AML. Therefore a major challenge is to find new drugs which are active in killing AML cells or which make AML cells more sensitive to the use of existing drugs. During Amber’s illness some of her blood was given for experimental testing. It was found that a chemical process was weakening the immune defense system and that this finding was worthy of further investigation.

 How has the Amber Phillpott Trust helped?

The Trust therefore gave funds to Oxford University to purchase an ELISA spectrometer. The spectrometer is a highly versatile piece of equipment which is able to highly accurately read the change in colour of liquid placed in the wells of an experimental plate. The University is investigating the mechanisms by which Acute Myeloid Leukaemia (AML) cells can interact with the immune system and allow AML cells to escape destruction. In addition they are trying to use novel drugs and effector cells to control the AML activity. The mechanisms that they are studying include the release of chemicals from AML cells and depletion of essential nutrients from the immune environment. These assays often use methods that result in a specific colour change hence the use of the spectrometer. The University has made significant and exciting progress in understanding how AML can dampen the immune response and has published their initial results in a paper in ‘BLOOD’ the Journal of the American Society of Hematology. See abstract at  

http://bloodjournal.hematologylibrary.org/content/122/5/749.long

To help further develop this new approach the Trust has made a donation to Birmingham University to assist in extending these early results. The current approach is to study how a nutrient called Arginine interacts with the leukaemic cell. Arginine is an essential nutrient that is taken in as part of our everyday diet. The University has strong preclinical evidence (laboratory and mouse model) that AML cells are reliant on arginine for critical cell processes that keep the AML cells alive. This pilot project will investigate for the first time, a) how AML cells take up arginine from their surroundings and b) whether blocking AML cells from using arginine will make them more sensitive to standard chemotherapy drugs. The results could provide a completely new way to target AML. Importantly this pathway could be targeted in all subtypes of AML, making a successful therapy widely applicable.