Leukaemia & Lymphoma

Using cutting edge genomic technologies, we are discovering and characterising both acquired and constitutional gene mutations (polymorphisms), which are improving our ability to predict disease onset, monitor treatment response and understand the mechanisms of relapse. 

We are developing targeted drug delivery based on novel gene mutations to improve the treatment of leukaemia and lymphoma by:

  • Using sophisticated functional assays to determine suitability as a drug target
  • RNA interference to ascertain their role as potential therapeutic targets

Research activities in leukaemia and lymphoma include:

Exploiting the leukaemic stem cell programme as a therapeutic target

Many cancers are believed to be maintained by a small population of highly specialised cancer stem cells. Cancer stem cells share similar characteristics with normal stem cells in that they are quiescent in nature, capable of self-renewal and give rise to daughter cells that are able to reconstitute the cancer cell population.

Our recent work has challenged this cancer stem cell model in childhood acute lymphoblastic leukaemia (ALL), and we have demonstrated the presence of leukaemic stem cell activity capable of extensive proliferation in a variety of lymphoid subpopulations.

We are currently exploring the biology of leukaemia stem cells to determine whether therapeutic interference with leukaemia specific mutations can produce targeted therapies with reduced toxicity.

We are fully integrated into the UK acute leukaemia clinical trial community and are curators of the Leukaemia and Lymphoma Research UK Cancer Cytogenetics Group Karyotype Database; this is the largest and most comprehensive trials based collection of genetic data world-wide.

Chromosome abnormalities present in the bone marrow cells of patients with leukaemia

Chromosome abnormalities have been found to be strongly linked to patient response to treatment. Recently, novel state-of-the-art molecular technologies, such as FISH analysis, have been introduced which have led to the discovery of a portfolio of chromosome changes.

This abnormality was found to be associated with poor survival rates in the ALL97 trial. Subsequently, treatment was intensified in iAMP21 patients enrolled in the ALL2003 UK trial, which improved clinical outcome and significantly reduced the number of relapse cases. Thus, treatment intensification may benefit patients with iAMP21 until alternative therapies are sought.

Research continues to determine the initiating mechanism responsible for iAMP21 in order to provide an improved diagnosis and targeted molecular therapy for this rare subgroup of ALL patients

Molecular screening of genetic abnormalities has been introduced into clinical trials. This has been highly successful, reducing the risk of relapse for patients with specific abnormalities, and the model is being extended to investigate lymphomas in both adults and children.