Leukaemia
Why we focus on Leukaemia
Leukaemias can be acute or chronic and arise from the myeloid or lymphoid lineage. The treatment of chronic myeloid leukamia (CML) has been revolutionised by the use of agents such as Imatinib that target the molecular basis of the disease and this has become the paradigm to develop novel targeted agents for all leukaemias.
Acute lymphoblastic leukaemia (ALL) is the most common cancer in children and is usually curable, however the outcome for adults is poor. Patients with ALL and high risk acute myeloid leukaemia (AML) are treated using intensive chemotherapy with stem cell transplant for those with an appropriate donor. However, many patients do not tolerate these therapies because of age and co-morbidity and the cure rate for those with poor risk disease is less than 10%. Therefore new approaches are desperately needed to improve patient outcome and to decrease the morbidity of treatment even in younger patients.
What we do
- We are characterising the nature of the leukaemic stem cells.
- We are investigating the interaction between normal and malignant stem cells. The focus of this work is to study how leukaemia out-competes normal haematopoietic stem cells to induce bone marrow failure.
- We are studying the molecular basis of familial leukaemia in order to understand the molecular evolution of disease.
- We are investigating the role and prognostic significance of sporadic mutations in disease, including analysis by whole genome sequencing approaches.
- We are studying the mechanisms whereby leukaemia induces immune suppression.
- We are investigating the nature of the graft versus leukaemia effect after allogeneic stem cell transplantation.
Key Publications
- Taussig et al. Leukemia-initiating cells from some AML patients with mutated nucleophosmin reside in the CD34(-) fraction. Blood 2010; 115: 1976-84.
- Le Dieu et al. Peripheral blood T cells in AML patients at diagnosis have abnormal phenotype and genotype and form defective immune synapses with AML blasts. Blood 2009; 114: 3909-16.
- Owen et al. Five new pedigrees with inherited RUNX1 mutations causing familial platelet disorder with propensity to myeloid malignancy. Blood 2008; 112: 4639-45.
- Ramsay et al. CLL T cells show impaired immunological synapse formation that can be reversed with an immunomodulating drug. J Clin Invest 2008; 118: 2427-37.
- Virappane et al. Mutation of the Wilms' tumor 1 gene is a poor prognostic factor associated with chemotherapy resistance in normal karyotype AML. J Clin Oncol 2008; 26: 5429-35.
Who does the research
→ Click here for BCI senior researchers working on leukaemia.
Major Funders
- Cancer Research UK
- Leukaemia & Lymphoma Research Fund
- Kay Kendall Leukaemia Fund
- MRC
- US NIH
