Childhood Leukaemia Research Group

anindita.roy@paediatrics.ox.ac.uk

MRC MHU

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.

Single cell transcriptomics reveals developmental stage and tissue specific composition of haematopoietic stem and progenitor cells. Image generated using SingCellaR (developed by S Thongjuea)

The focus of research in the Childhood Leukaemia group is to study prenatal B lymphopoiesis in order to understand the origins of childhood leukaemia (Jackson, Ling and Roy 2021), 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 (Popescu et al, 2019; Hua et al, 2019, Roy et al 2021, Jardine, Webb et al 2021) 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, 2021) 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, 2021). 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.