Research

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.

Other Activities

• Member of the National Cancer Institute Adult ALL subgroup

Major Funding

• 2018-2020- Blood Cancer UK, Unravelling mechanisms of tumour dormancy in adult lymphoblastic leukaemia (ALL), £510,644
• 2016-2021- Cancer Research UK, Personalising therapy for adults with acute lymphoblastic leukaemia, £208,076.47
• 2015-2018- Blood Cancer UK, Mechanisms of Tumour Dormancy in Adult Acute Lymphoblastic, £737,787 (Renewal 2018)

Recent Publications

Genetic and genomic analysis of acute lymphoblastic leukaemia in older adults reveals a distinct profile of abnormalities: analysis of 210 patients from the UKALL14 and UKALL60+ clinical trials. Creasey T, Barretta E, Ryan SL et al. Haematologica (2021) (2)
https://www.ncbi.nlm.nih.gov/pubmed/34788984

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)
https://www.ncbi.nlm.nih.gov/pubmed/32420609

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

Team

Clinical Research Fellows
Dr Fiona Fernando 

Research Technician
Ionela Pislariu 

Biography

I undertook my medical studies at Imperial College of Science Technology and Medicine.