Acute Myeloid Leukaemia Research

Leukaemia is a cancer affecting white blood cells which form part of the body's defence against infection. It accounts for 2% of newly diagnosed cancers in the UK, approximately 6,600 cases each year.

Acute leukaemia is a form of the disease that can progress very rapidly whereas chronic leukaemia usually progresses slowly. In acute leukaemia, immature white blood cells accumulate in the body and can interfere with the normal functioning of tissues and organs. There are two types of acute leukaemia depending upon the types of white blood cells affected:

• Acute lymphoblastic leukaemia (ALL)
• Acute myeloid leukaemia (AML)

Acute myeloid leukaemia (AML) affects approximately 2,000 adults and 50 children per year in the UK. In this form of the disease, there is an overproduction of immature myeloid white blood cells (blast cells). These cells fail to repair and reproduce themselves in a controlled way but continue to divide without maturing correctly. As a consequence, these immature cells fail to work properly leaving the body vulnerable to infection. In addition, the immature cells fill up the bone marrow preventing it from manufacturing healthy blood cells.

The Nottingham City Hospital and the University of Nottingham's Department of Academic Haematology, led by Professor Nigel Russell has conducted research in to AML and other forms of leukaemia for many years. Dr. Claire Seedhouse and her colleagues are investigating two particular aspects of AML:

• Drug Resistance - Why do some patients develop a disease which is resistant to the cytotoxic effects of chemotherapy? Is there a particular genetic make-up associated with this resistance?
• DNA Repair - Can defects in DNA repair processes lead to AML? Are people with certain genetic make-ups more susceptible to AML?

An important tool in this research is the Comet Assay, which is used increasingly in medical research and diagnosis. Dr. Seedhouse uses the assay to measure DNA damage in lymphocytes and leukaemic blast cells following chemotherapy. Neutral and alkaline versions of the assay are performed using commercially available slides and reagents from Trevigen.

Comet slides are stained with propidium iodide and examined using a fluorescence microscope (Olympus) equipped with an excitation filter (510-550 nm) with a 20x objective. Analysis is performed using the Comet Assay III scoring system from Perceptive Instruments. Images from the microscope are displayed live on the computer display and nucleoids are individually scored. Typically 50 cells are analysed per slide with two slides for each treatment dose. At the magnifications involved, there are typically about ten nucleoids in the image enabling analysis to be conducted quickly and efficiently.

The research is still progressing, however it is planned that findings will be published in the near future.

Useful links

www.lrf.org.uk
www.cancerbackup.org.uk
www.cancerresearchuk.org

Contact

Dr. Claire Seedhouse - claire.seedhouse@nottingham.ac.uk