We are investigating the link between human fetal haematopoiesis and the origin and biology of childhood leukaemia. In particular, we are interested in the pathogenesis of infant leukaemia, which is a refractory disease that invariably originates in utero.
The focus of research in the Childhood Leukaemia group is to study prenatal B lymphopoiesis in order to understand the origins of childhood leukaemia, in particular infant acute lymphoblastic leukaemia (ALL). Infant ALL invariably originates before birth and MLL gene rearrangement is often sufficient to cause leukaemic transformation without additional genetic abnormalities. Our research aims to identify and characterise the poorly understood target cell population responsible for in utero initiation of infant ALL. We have previously identified a specific population of prenatal B progenitors that co-exist with adult-type B progenitors. These transient B progenitors that proliferate in a developmental stage and site-specific manner are likely to be the target for MLL rearrangements in a defined prenatal time window. We now want to better define the B lymphoid developmental hierarchy before birth; and characterise the unique prenatal B progenitors by detailed immunophenotypic, functional and molecular studies in order to determine whether they may be a substrate for leukaemia initiating hits in infant ALL. This approach will allow us to identify pathways that can be targeted for future therapies in infant ALL.
Dr Roy is also a member of Prof Irene Roberts’ team investigating how trisomy 21 perturbs haematopoiesis before birth and its implications for Down syndrome associated leukaemias in children, in particular DS-ALL.
Prof Irene Roberts, Department of Paediatrics, University of Oxford
Prof Thomas Milne, Weatherall Institute of Molecular Medicine, University of Oxford
Prof Adam Mead, Weatherall Institute of Molecular Medicine, University of Oxford
Dr Bethan Psaila, Weatherall Institute of Molecular Medicine, University of Oxford
Prof Tassos Karadimitris, Centre for Haematology, Imperial College London
Prof Benedikt Kessler, Nuffield Department of Medicine, University of Oxford
Prof Pablo Menendez, University of Barcelona, Barcelona, Spain
Dr Valentina Caputo, Centre for Haematology, Imperial College London
Dr Philip Ancliff, Great Ormond Street Hospital, London
Ms Sarah Inglott, Great Ormond Street Hospital, London
Dr Adam de Smith, UCSF, San Francisco, USA