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Lymphoma

Leukemia Microenvironment

Team Leader

Dr Andrea Buggins
Research Associate
Email:andrea.buggins@kcl.ac.uk
Tel: +44 (0)20 7848 5803

Research Overview

Following time as a biomedical scientist I moved into research and did a Ph.D. on the effect of the microenvironment in acute Myeloid leukaemia (AML). For the past 10 years my research career has been focused on one disease, chronic lymphocytic leukaemia (CLL), again with a major focus on the role of the microenvironment. CLL represents an unrivalled primary human tumour model for investigating apoptosis, activation and migration and these areas of investigation have been the focus of my team. We have used primary CLL cells to demonstrate both the anti-apoptotic effect of endothelial cells (via the NF-kB pathway) and activation effect of normal CD4+ T cells on their survival and proliferation. The role of T cells in CLL is a major component of our research and as well as identifying the stimulatory effect they can have on the tumour, we have also shown that CLL cells promote their own survival by secreting high levels of IL-6 which has an immunosuppressive effect on T cells thus inhibiting anti-tumour effector responses.  We have also adopted the fine needle aspirate technique to enable us to obtain matching tissue from patient’s lymph nodes and peripheral blood and compare phenotypic and functional differences in the T and CLL cells that reside within the two compartments. In addition to these studies, we have investigated the biological role of antigens associated with poor prognosis in CLL (CD38 and CD49d etc.) and demonstrated they are physically linked.  These studies have resulted in publications in BLOOD, Cancer Research, Leukemia and British Journal of Haematology. 

Most recently, we have begun to expand and address questions relating to B-cell receptor signalling and the effect of drugs on the T and B cell interactions. In addition, we have extended our disease base to include other Lymphomas and are currently studying the role of T cells in follicular lymphoma. For future work we will expand further into the biology of high and low grade lymphomas, utilise the skills and knowledge we have from our work on CLL, and also look at signalling through toll like receptors.

Our research is entirely patient-focused; predominately based on primary CLL cells derived from patients and even our basic research has a strong translational element designed to improve patient care.

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Key co-investigators and collaborators
King's College London
Professor Stephen Devereux
Dr Piers Patten
Dr Alan Ramsay
Dr Linda Barber
Professor Anne Ridley

Cardiff University
Professor Chris Pepper
Professor Duncan Baird

Professor Simon Jones

Recent Grants
An investigation of the effect of cyclosporine-A in chronic lymphocytic leukaemia: development of a novel in-vivo strategy for dissecting the mechanism of drug action
Leukaemia & Lymphoma Research
Devereux, S., Buggins, A.
£129,228
1/04/13 → 31/03/15
Research Project

Dissecting the Role of T-cells in the Pathogenesis of Chronic Lymphocytic Leukaemia. An in-vitro and in-vivo investigation
Kay Kendall Leukaemia Fund
Devereux, S., Buggins, A., Tree, T.
£212,588
1/02/13 → 31/01/16
Research Project

An investigation of the CD4+ T cell compartment in follicular Lymphoma
British Society for Haematology

Buggins, A., Devereux, S.
£15,000
1/01/13 → 31/12/15
Research Project

An investigation of the effect of cyclosporine-A in chronic lymphocytic leukaemia: development of a novel in-vivo strategy for dissecting the mechanism of drug action

Leukaemia & Lymphoma Research
Devereux, S., Buggins, A.
£50,180
1/12/12 → 30/11/15
Research Fellowship

An investigation into the T cell compartment of Follicular Lymphoma
Leukaemia & Lymphoma Research

Devereux, S., Buggins, A., Tree, T.
£28,831
1/03/11 → 31/03/15

Research Project

Selected Publications

  1. Walsby E, Buggins A, Devereux S, Jones C, Pratt G, Brennan P, Fegan C, Pepper C. Development and characterization of a physiologically relevant model of lymphocyte migration in chronic lymphocytic leukemia. Blood. 2014 Jun 5;123(23):3607-17.
  2. Andrea G.S. Buggins2*, Chris Pepper1*, Ceri H. Jones1, ElisabethJ. Walsby1, Francesco Forconi3, Guy Pratt4, Stephen Devereux2, Freda K.Stevenson3, Chris Fegan.Phenotypic heterogeneity in IGHV mutated CLL patients has prognostic impact and identifies a subset with increased sensitivity to BTK inhibition. In Press 2014.
  3. Hamilton E, Pearce L, Morgan L, Robinson S, Ware V, Brennan P, Thomas NS, Yallop D, Devereux S, Fegan C, and *, Pepper C* and Buggins A.G.S* Joint senior author. Mimicking the tumour microenvironment: three different co-culture systems induce a similar phenotype but distinct proliferative signals in primary chronic lymphocytic leukaemia cells. Br J Haematol. 2012 Sep;158(5):589-99.
  4. Buggins AG, Levi A, Gohil S, Fishlock K, Patten PE, Calle Y, Yallop D, Devereux S.  Evidence for a macromolecular complex in poor prognosis CLL that contains CD38, CD49d, CD44 and MMP-9. Br J Haematol. 2011 May 14.1365-2141.
  5. Pepper C*, Mahdi JG*, Buggins AG≠, Hewamana S, Walsby E, Mahdi E, Al-Haza'a A, Mahdi AJ, Lin TT, Pearce L, Morgan L, Bowen ID, Brennan P, Fegan C. Two novel aspirin analogues show selective cytotoxicity in primary chronic lymphocytic leukaemia cells that is associated with dual inhibition of Rel A and COX-2. Cell Prolif. 2011 Jun 6. 1365-2184 .* Joint first authors ≠ second author.
  6. Buggins AG, Pepper C, Patten PE, Hewamana S, Gohil S, Moorhead J, Folarin N, Yallop D, Thomas NS, Mufti GJ, Fegan C, Devereux S.  Interaction with vascular endothelium enhances survival in primary chronic lymphocytic leukaemia cells via NF-kappaB activation and de novo gene transcription. Cancer Res. 2010 Oct 1;70(19):7523-33.
  7. Majid A, Lin TT, Best G, Fishlock K, Hewamana S, Pratt G, Yallop D, Buggins AG, Wagner S, Kennedy BJ, Miall F, Hills R, Devereux S, Oscier DG, Dyer MJ, Fegan C, Pepper C.  CD49d is an independent prognostic marker that is associated with CXCR4 expression in CLL. Leuk Res. 2010 Nov 17.
  8. Buggins AG, Pepper CJ. The role of Bcl-2 family proteins in chronic lymphocytic leukaemia. Leuk Res. 2010 Jul;34(7):837-42.
    Buggins AG, Patten PE, Richards J, Thomas NS, Mufti GJ, Devereux S. Tumor-derived IL-6 may contribute to the immunological defect in CLL. Leukemia. 2008 May;22(5):1084-7.
  9. Patten PE, Buggins AG, Richards J, Wotherspoon A, Salisbury J, Mufti GJ, Hamblin TJ, Devereux S. CD38 expression in chronic lymphocytic leukemia is regulated by the tumor microenvironment. Blood. 2008 May 15;111(10):5173-81.
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