Professor Mel Greaves FRS

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

Melvyn (Mel) Greaves is working to unravel the causes of childhood leukaemia by examining the genetic influences and biological pathways that lead to the disease.

Professor Greaves has worked at the ICR since 1984, when he joined to establish the UK’s first Leukaemia Research Fund Centre (for Cell and Molecular Biology). Earlier in his career, Professor Greaves pioneered immunological methods to differentiate between types of leukaemia, which improved understanding of the disease and allowed treatments to be better tailored to patients.

Professor Greaves and his team made a major discovery at the ICR in the 1990s when studies on identical twins and neonatal blood spots identified mutations that initiated leukaemia before birth. He has been trying to work out what triggers the clinical emergence of leukaemia when children are between two and five years old, and has accumulated evidence that incriminates an abnormal immune response to infection and the cytokine molecule TGF beta.

Professor Greaves says a major goal is to confirm the role that common childhood infections play in the development of leukaemia. He is looking for more evidence that children exposed to infections as babies develop a normal immune response and receive some protection against leukaemia, while children who are not exposed until later in life – generally those from affluent societies - are at higher risk. Inherited susceptibility also plays a role, and Professor Greaves is studying this in collaboration with the ICR’s Section of Genetics. Evolutionary principles provide a key framework for these studies.

Professor Greaves has a broad educational background, initially training in zoology and immunology in the sixties at University College in London and Stockholm. He was drawn into cancer research in the mid-1970s when, as a young father, he visited a cancer ward at a London hospital and met children stricken with leukaemia. At the time, little was known about the disease, and Professor Greaves began a lifelong study – initially at the Imperial Cancer Research Fund (now the Cancer Research UK London Research Institute) - into its biology in the hope of improving patient diagnosis, treatment options and ultimately prevention.

His research at the ICR has been recognised by many national and international awards including the José Carreras Award, the British Society for Haematology Gold Medal and the King Faisal International Prize for Medicine. Professor Greaves is an Honorary Member of the Royal College of Physicians, a Fellow of the United Kingdom Academy of Medical Sciences and was elected to The Royal Society in 2003.

Outside leukaemia research, Professor Greaves has broad and eclectic interests in evolutionary biology, cancer and medicine, and wrote the popular science book Cancer: The Evolutionary Legacy (Oxford University Press), which has been translated into five foreign languages and Braille. His latest book is White Blood: Personal Journeys with Childhood Leukaemia (World Scientific). Professor Greaves  enjoys classical music, opera, the theatre, many sports (all too passively now) and being a grandfather.