Dr Bela Wrench

MBBS, MD (Res), MRCP, FRCPath
Clinical Senior Lecturer
Senior Bennett Fellow
Group Leader
Research Focus

My research focuses on the fundamental aspects of leukaemia initiating cell biology in adult acute lymphoblastic leukaemia.

Key Publications

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

Major Funding
  • 2018-2020- Bloodwise, 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- Bloodwise, Mechanisms of Tumour Dormancy in Adult Acute Lymphoblastic, £737,787 (Renewal 2018)

Other Activities
  • Member of the National Cancer Institute Adult ALL subgroup
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- Bloodwise, 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- Bloodwise, Mechanisms of Tumour Dormancy in Adult Acute Lymphoblastic, £737,787 (Renewal 2018)
Recent Publications

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. Mol Ther (2016) 24(2) 184-192
https://www.ncbi.nlm.nih.gov/pubmed/26278331

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(11)
http://gateway.webofknowledge.com/gateway/Gateway.cgi?GWVersion=2&SrcApp=PARTNER_APP&SrcAuth=LinksAMR&KeyUT=WOS:000368020102130&DestLinkType=FullRecord&DestApp=ALL_WOS&UsrCustomerID=612ae0d773dcbdba3046f6df545e9f6a

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(2) 96-105
https://www.ncbi.nlm.nih.gov/pubmed/24825861

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(2) 1327-1335
https://www.ncbi.nlm.nih.gov/pubmed/24345754

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(2) 843-850
https://www.ncbi.nlm.nih.gov/pubmed/24277073

IGH@ translocations, CRLF2 deregulation, and microdeletions in adolescents and adults with acute lymphoblastic leukemia. Moorman AV, Schwab C, Ensor HM et al. J Clin Oncol (2012) 30(2) 3100-3108
https://www.ncbi.nlm.nih.gov/pubmed/22851563

Attenuated, oncolytic, but not wild-type measles virus infection has pleiotropic effects on human neutrophil function. Zhang Y, Patel B, Dey A et al. J Immunol (2012) 188(2) 1002-1010
https://www.ncbi.nlm.nih.gov/pubmed/22180616

Differential cytopathology and kinetics of measles oncolysis in two primary B-cell malignancies provides mechanistic insights. Patel B, Dey A, Ghorani E et al. Mol Ther (2011) 19(2) 1034-1040
https://www.ncbi.nlm.nih.gov/pubmed/21427708

For additional publications, please click here
Team

Postdoctoral Researchers
Dr Chrysi Xintaropoulou, Dr Quentin Heydt

Clinical Research Fellows
Dr Fiona Fernando 

Research Technician
Ionela Pislariu 

Biography

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.