David G
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20 years of success for the Leukaemia & Lymphoma Research Cytogenetics Database

David G
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28 Mar 2012

A two-day meeting held in Newcastle last week celebrated the success of 20 years of funding of a project by Leukaemia & Lymphoma Research which has made a huge contribution to saving the lives of many children diagnosed with acute lymphoblastic leukaemia (ALL).

In 1990 Professor Lorna Secker-Walker, an expert in cytogenetics (the study of chromosomes), asked this charity to fund a national database to collect and analyse the chromosomal abnormalities found in children diagnosed with ALL.

The rationale was that whilst most children exhibited a chromosomal abnormality, the small number of patients analysed at each regional laboratory made it impossible to determine how this affected the biology of the disease or the likely outcome of treatment.  Professor Secker-Walker reasoned that if the results from all 550 children diagnosed each year in the UK could be analysed together, then reliable and reproducible patterns would emerge to enable scientist to predict how well or how poorly children would respond to treatment. 

Over the following 20 years this has proved to be spectacularly correct, with children being assessed very early in their treatment to decide whether they were likely to be cured by standard chemotherapy, required more intensive chemotherapy or should undergo stem cell transplantation. This coincided with the realisation that the “one size fits all” approach to cancer treatment was no longer tenable and approaches that were much more patient specific had to be developed based on the genetic abnormalities found in the leukaemia cells.

In 1997, Professor Christine Harrison took over as director of the project and over the subsequent 15 years has taken the success of the research to new levels. Two strategies have been key to the advancement of the project: the application of state-of-the-art technologies to identify new genetic abnormalities and the extension of the database to include adult ALL and childhood and adult acute myeloid leukaemia (AML).

The database now holds information on more than 28,000 patients with acute leukaemia and has been instrumental in defining treatment approaches based on genetic abnormalities in all current UK clinical trials for acute leukaemia.

One important chromosomal abnormality discovered within the project is the so-called “intrachromosomal amplification of chromosome 21” or iAMP21. This abnormality is associated with a poor outcome in childhood ALL and patients with this abnormality are now successfully treated with more intensive chemotherapy.

Pictured (right) is a leukaemia cell from a patient with iAMP21, indicating how the abnormality is identified. The individual chromosomes are depicted in blue. The two copies of chromosome 21 are highlighted by red signals. The normal chromosome 21 shows just one pair of signals, whereas the abnormal chromosome 21 harbours multiple signals along its entire length indicative of iAMP21.

Dr David Grant had been Scientific Director of Leukaemia & Lymphoma Research since 1990, during which time he had overseen a huge increase in investment into life-saving research. He is retiring this month and will be succeeded by Professor Chris Bunce, joining from his current role as a researcher at The University of Birmingham.