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). 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’ team investigating how trisomy 21 perturbs haematopoiesis before birth and its implications for Down syndrome associated leukaemias in children, in particular DS-ALL.
Our team
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Anindita Roy
Associate Professor of Paediatric Haematology
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Natalina Elliott
Postdoctoral Researcher
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Thomas Jackson
Postdoctoral Research Scientist
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Siobhan Rice
DPhil Student
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Caitlin Murnane
DPhil Student within Developmental Haematology and Paediatric Leukaemia Group
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Rebecca Ling
DPhil student
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Sorcha O'Byrne
DPhil Student
Current opportunities available
Postdoctoral opportunities to be advertised Jan-Feb 2021.
Latest news
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.
Feb 2021: New paper in collaboration with Adam deSmith (USC): Muskens et al. The genome-wide impact of Trisomy 21 on DNA methylation and its implications for hematopoiesis
Jan 2021: New paper out in print in collaboration with Milne lab: Godfrey L, Crump N et al. H3K79me2/3 controls enhancer–promoter interactions and activation of the pan-cancer stem cell marker PROM1/CD133 in MLL-AF4 leukemia cells.
Dec 2020: Congratulations to Siobhan Rice for winning an ASH abstract achievement award.
Collaborations
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
Dr S Thongjuea, Weatherall Institute of Molecular Medicine, University of Oxford
Prof Tassos Karadimitris, Centre for Haematology, Imperial College London
Prof Muzlifa Haniffa, Newcastle University
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