Childhood Leukaemia Research Group
Founded in 2015
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 poor prognosis subtypes such as 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 (Rice and Roy, 2020). Our research aims to identify and characterise the poorly understood target cell population responsible for in utero initiation of infant ALL. In order to understand the origins of infant ALL we have characterised prenatal human B cell hierarchy for the first time (O'Byrne et al, 2019), thereby identifying specific ontogeny related developmental programmes and a possible fetal specific target cell for infant ALL. Through several collaborative projects, we use functional and molecular single cell approaches to understand human haematopoiesis (Psaila et al, 2016; Popescu et al, 2019; Hua et al, 2019) These data are crucial in understanding how changes in B lymphopoiesis through the human lifetime influence the biology of leukaemias that originate at different ages. We now want to 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. To do this we have developed novel leukaemia models by transforming human fetal progenitor cells using CRISPR-Cas9 mediated chromosomal translocations (Rice et al, 2020) in collaboration with the Milne lab. This approach will allow us to identify pathways that can be targeted for future therapies in infant ALL (Godfrey, Crump et al, 2020; Harman et al, 2020). We also aim to create a low-cost model of care for infant ALL in resource-poor settings, and have started collaboration with centres in India in order to deliver this.
We work closely with Prof Irene Roberts investigating how trisomy 21 perturbs haematopoiesis before birth and its implications for Down syndrome associated leukaemias in children, in particular DS-ALL.
Current opportunities available
Postdoctoral opportunities to be advertised March 2021.
Feb 2021: Short interview with Congenital Anaemia Network about our research in infant ALL on Rare Disease Day 2021
Feb 2021: Celebrating 100 years of Oxford Degrees for women. 100 Women of Oxford Medical Sciences Feature
Feb 2021: New review in Frontiers in Immunology: Jackson TR, Ling R, Roy A. The origin of B-cells: Human fetal B cell development and implications for the pathogenesis of childhood acute lymphoblastic leukemia.
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
Prof Tassos Karadimitris, Centre for Haematology, Imperial College London
Prof V Saha, Tata Medical Centre, Kolkata, India
Dr Philip Ancliff, Great Ormond Street Hospital, London
Ms Sarah Inglott, Great Ormond Street Hospital, London
Prof Adele Fielding, University College London, London
Prof Anthony Moorman, Newcastle University
Prof Pablo Menendez, University of Barcelona, Barcelona, Spain
Prof Jonathan Bond, University of Dublin, Ireland
Dr Adam de Smith, UCSF, San Francisco, USA
Prof Benedikt Kessler, Nuffield Department of Medicine, University of Oxford