Biology of Childhood Leukaemia
Our specialist programme of research (funded by The Kay Kendall Leukaemia Fund and Leukaemia & Lymphoma Research) seeks to uncover the pre-clinical natural history, clonal evolution and aetiology of the major subtype of paediatric leukaemia: childhood acute lymphoblastic leukaemia (ALL).
Individual projects in the portfolio are designed to endorse developmental models for these leukaemias involving pre-natal initiation and a trigger for overt clinical disease involving abnormal immune responses to infection.
We have an extensive network of UK-based and international collaborators providing access to patient samples. Our epidemiological interests are pursued via the UK Children’s Cancer Study Group (UKCCS) and via international cooperation (e.g. Brazil, Hong Kong, Japan and Italy). Our genetic studies on inherited susceptibility to ALL are pursued in collaboration with Professor Richard Houlston and colleagues in the Genetics Section of the Institute of Cancer Research (ICR).
Key review references to team’s work:
- Greaves, MF (2006) Infection, immune responses and the aetiology of childhood leukaemia. Nature Reviews Cancer, 6: 193-203
- Greaves MF, Maia AT, Wiemels JL, Ford AM (2003) Leukemia in twins: lessons in natural history. Blood, 102: 2321-2333
- Greaves MF, Wiemels J (2003) Origins of chromosome translocations in childhood leukaemia. Nature Reviews Cancer, 3: 639-649
- Greaves M (2007) Darwinian medicine: a case for cancer. Nat Rev Cancer, 7: 213-221
- Ford AM, Palmi C, Bueno C, Hong D, Cardus P, Knight D, Cazzaniga G, Enver T, Greaves M (2009) The TEL-AML1 leukemia fusion gene dysregulates the TGF pathway in early B lineage progenitor cells. J Clin Invest, 119: 826-836
- Papaemmanuil E, Hosking FJ, Vijayakrishnan J, Price A, Olver B, Sheridan E, Kinsey SE, Lightfoot T, Roman E, Irving JAE, Allan JM, Tomlinson I, Taylor M, Greaves M, Houlston RS (2009) Loci on 7p12.2, 10q21.2 and 14q11.2 are associated with risk of childhood acute lymphoblastic leukemia. Nature Genet, 41: 1006-1010
- Anderson K, Lutz C, van Delft FW, Bateman CM, Guo Y, Colman SM, Kempski H, Moorman AV, Titley I, Swansbury J, Kearney L, Enver T, Greaves M (2011) Genetic variegation of clonal architecture and propagating cells in leukaemia. Nature, 469: 356-361