My research focuses on the fundamental aspects of leukaemia initiating cell biology in adult acute lymphoblastic leukaemia.
Toxicity During Induction Therapy in Adults With Newly Diagnosed Acute Lymphoblastic Leukaemia (ALL): Results From the UK Multicentre Trial UKALL14. Leukemia (2017) 31, 58-64. PMID: 27480385
Mouse xenograft modelling of Human Adult Acute Lymphoblastic Leukaemia provides mechanistic insights into adult LIC biology. Blood (2014) 124(1): 96-105. PMID: 24825861
Human mesenchymal stromal cells deliver systemic oncolytic measles virus to treat acute lymphoblastic leukemia in the presence of humoral immunity. Blood (2014) 123(9):1327-35. PMID: 24345754
Differential Cytopathology and Kinetics of Measles Oncolysis in Two Primary B-cell Malignancies Provides Mechanistic Insights. Mol Ther (2011) 19(6):1034-40. PMID: 21427708
Attenuated, oncolytic, but not wild-type measles virus infection has pleiotropic effects on human neutrophil function. J Immunol (2012) 188(3):1002-10. PMID: 22180616
Leukaemia initiating cells (LIC) are required for initiation and maintenance of leukaemic growth.
Current therapies fail to target these deleterious subsets resulting in a persistent risk of relapse. My group's overarching aim is to gain fundamental insight into the underlying biology of LICs with the aim of revealing dependencies that are tractable targets for therapy.
My previous work established the dominance of “niche” derived factors in driving LIC activity over cell intrinsic oncogenes providing a rationale for niche based therapy. Our ongoing studies aim to evolve our understanding of the role of microenvironment in determining the phenotypes of LIC’s, in particular cellular dormancy, an essential mechanism conferring chemo protection.
Using tractable xenotransplanation models, cellular imaging, high resolution genomics and proteomics, we aim to provide a comprehensive and coherent portrait of the complex biology of ALL- LICs with the overall aim of informing strategies for minimising leukaemia recurrence.
My laboratory interests are complimented by my clinical expertise in adult ALL (Honorary Consultant, Dept of Haemato-Oncology, St Bartholomew’s hospital). I am a member of the National Cancer Research Institute adult ALL subgroup which leads the UK’s clinical trial portfolio.
Adipocytes disrupt the translational programme of acute lymphoblastic leukaemia to favour tumour survival and persistence Heydt Q, Xintaropoulou C, Clear A et al. Nature Communications (2021) (1)
Clinical Outcome of Coronavirus Disease 2019 in Haemato-oncology Patients. Aries JA, Davies JK, Auer RL et al. British Journal of Haematology (2020) (1)
Genomic analyses identify recurrent MEF2D fusions in acute lymphoblastic leukemia WRENCH BR Nature Communications (2017) 7(1)
Pegylated-asparaginase during induction therapy for adult acute lymphoblastic leukaemia: toxicity data from the UKALL14 trial WRENCH BR leukaemia (2017) (1)
The role of neutrophils in measles virus-mediated oncolysis differs between B-cell malignancies and is not always enhanced by GCSF Dey A, Zhang Y, Castleton AZ et al. Molecular Therapy (2016) 24(7) 184-192
High Frequency and Poor Outcome of Ph-like Acute Lymphoblastic Leukemia in Adults Roberts KG, Payne-Turner D, McCastlain K et al. Blood (2015) 126(10) 2618-2618
Mouse xenograft modeling of human adult acute lymphoblastic leukemia provides mechanistic insights into adult LIC biology Patel B, Dey A, Castleton AZ et al. Blood (2014) 124(7) 96-105
Human mesenchymal stromal cells deliver systemic oncolytic measles virus to treat acute lymphoblastic leukemia in the presence of humoral immunity Castleton A, Dey A, Beaton B et al. Blood (2014) 123(7) 1327-1335
UKALLXII/ECOG2993: Addition of imatinib to a standard treatment regimen enhances long-term outcomes in Philadelphia positive acute lymphoblastic leukemia Fielding AK, Rowe JM, Buck G et al. Blood (2014) 123(7) 843-850
IGH@ translocations, CRLF2 deregulation, and microdeletions in adolescents and adults with acute lymphoblastic leukemia Moorman AV, Schwab C, Ensor HM et al. Journal of Clinical Oncology (2012) 30(7) 3100-3108For additional publications, please click here
Clinical Research Fellows
Dr Fiona Fernando
I undertook my medical studies at Imperial College of Science Technology and Medicine.
After general post-graduate medical training I decided to sub-specialise in Haematology, inspired by the opportunity to link laboratory diagnostics with clinical care in a meaningful way.
In 2005 I joined Professor Letizia Foroni’s Laboratory at University College London to undertake MD research into adult ALL and MRD resistance. Subsequently, in 2008, I was awarded an intermediate Clinician Scientist Fellowship (Bloodwise) where I investigated mechanisms regulating adult leukaemia initiating cell activity.
In 2014 I joined BCI as a clinical senior lecturer to establish my own research group.