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The University of Southampton
Medicine

Dr Francesco Forconi MD, DM, PhD, FRCPath

Associate Professor in Haematological Oncology, Honorary Consultant Haematologist

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Dr Forconi is a clinical haemato-oncologist and cancer immunologist. His group investigates the pathogenesis of mature B-cell lymphomas and chronic lymphocytic leukaemias, with focus on the structure and the function of the tumour B-cell receptor, to refine their prognosis and therapy.

As a clinician and scientist, I aim to translate new knowledge from bench to bedside and to improve the lives of patients with haematological cancers. My research investigates the key molecules that govern the behaviour of cancer B lymphocytes and that can be targeted therapeutically in patients with lymphomas and leukaemias.

Dr Francesco Forconi graduated in medicine (summa cum laude) in 1996 and completed his specialist training in haematology (70/70 cum laude) in 2003 at the University of Siena, Italy. He intercalated his clinical training with a research fellowship in lymphoma at the University of Turin in Novara in 1998, and with a 3 year PhD programme in cancer B-cell immunology at the Tenovus Laboratories, University of Southampton, that he completed in 2002. In 2004 he was appointed as Professor Assistant and Consultant in Haematology at the University of Siena Hospital Trust, before moving back to Southampton in 2011.

Dr Forconi is the clinical scientific lead of the Academic B-cell Group at the School of Cancer Sciences, where he interacts with world-class PIs and scientists investigating microenvironmental interactions, cell signalling, (epi)genetics, and novel therapies of B-cell tumours. His Haematological Oncology Research Group focuses on the behaviour of mature B-cell neoplasms by analysis of the structure and function of the tumour B-cell receptor (BCR) in the most common leukaemia (Chronic lymphocytic leukaemia - CLL) and lymphomas (Follicular lymphoma and Diffuse large B-cell lymphomas). He is currently the author of >140 publications (>9700 citations, >1000 impact factor, h-index 49, i10-index 124) and leads several collaborative scientific projects nationally and internationally in Lymphoma and CLL, including the recent CRUK ECRIN-M3 accelerator programme on monoclonal B-cell lymphocytosis with international partners (2020-2025).

His clinical activity is primarily dedicated to the care of patients with lymphomas and CLL. In Southampton, he leads the lymphoid clinic service and is a UK chief investigator an/or a principal investigator in several phase I/II/III clinical trials using novel therapeutic agents against lymphomas/leukaemia.

Dr Forconi has been a member of the UK NCRI Haematological Oncology Clinical Studies Group and regularly engages actively with the UK NCRI CLL Subgroup. He has served the UK National Institute for Clinical Excellence (NICE) for several technology appraisals for novel agents in the clinical practice. He is an active core member of the Hairy Cell leukemia Foundation, USA and leads Southampton as a “Center of Excellence” for Hairy Cell Leukemia.  He is Editorial Board Member for Blood and regularly contributes as a reviewer for the major journals of clinical and scientific immunology, oncology and haematology, has chaired sessions at major international conferences including the American Society of Hematology (ASH) annual meetings, and has provided educational contributions at major haemato-oncology meetings including UK CLL forum, EHA, ASH, and ECCO/ESMO.

Qualifications

MD, Medicine and Surgery, University of Siena, Italy 1996

DM, Cancer Immunology, University of Southampton, 2001

PhD, University of Siena, Italy 2002

Specialist Haematologist, University of Siena, 2003

FRCPath, Royal College of Pathologists, London, 2013

Appointments held.

2004-2011 Professore Aggregato (Lecturer/Reader) and Consultant Haematologist, University of Siena, Italy

2011-2014 Senior Lecturer and Consultant Haematologist, University of Southampton, UK

Forconi group
Forconi group

Research interests

The B-Cell Receptor (BCR) is the functional unit and unique to any normal B-cell. Its characteristics and functions are preserved after transformation and provide insight in the origin and clinical behaviour of the transformed B-cell. The overall research goal of the Haematological Oncology group is to investigate origin and mechanisms of disease of B-cell lymphomas by analysis of the tumour BCR Immunoglobulin (Ig) characteristics and function.

The group will focus on Chronic lymphocytic leukaemia (CLL). The variable clinical course of the two major CLL subsets expressing unmutated or mutated Ig genes (U-CLL and M-CLL, respectively) and the dramatic sensitivity of CLL to inhibitors of BCR-signalling associated kinases highlight the central role of the tumour BCR. CLL cells express low levels of surface Ig (sIg) as a reflection of anergy. However individual circulating cells overexpressing bcl2 will survive and variably recover function to eventually migrate to tissue either for repetitive rounds of antigen-mediated proliferation, and possible secondary genetic damages determining further variability in outcome in the functionally recovered CLL cells, or for sustainment of the anergic CLL cells.

One of our projects is to investigate the functional complexity within individual CLL clones defined by B-cell receptor (BCR) level dynamics. Surface IgM (sIgM) is down-modulated following engagement but recovery of expression occurs in vitro, and likely in vivo during recirculation. We can readily identify circulating intraclonal subgroups with varying B-cell receptor expression and function in CLL (Coelho et al. Blood, 2013). Aims of this project will be to investigate the phenotypic, functional and molecular features associated with survival/proliferation, migration and immune suppression in each individual CLL subgroups and the dynamics of recirculation between tissues and blood.

A second project is to investigate and to target therapeutically the mechanisms of immune suppression in CLL. BCR signalling is likely to contribute to the immunosuppression which is the main cause of morbidity and mortality in CLL. Recent clinical data demonstrate that new inhibitors of BCR-associated kinases reverse immunosuppression in the initial phases of treatment. Our recent data have confirmed that BCR stimulation modulates immunoregulatory properties of CLL cells. This programme will therefore address the hypothesis that BCR signalling is a key determinant of immune suppression in CLL and possibly in other B-cell malignancies. Current specific aims are (i) to investigate the immunoregulatory phenotype of CLL cells in the presence/absence of BCR stimulation; (ii) to characterise functional consequences of BCR stimulation on immunoregulatory properties of CLL cells; (iii) to investigate effects of novel drugs targeted towards BCR-associated kinases in vitro and in vivo; (iv) to determine the clinical significance of immunoregulatory properties. Stimuli will include various forms of anti-Ig ±costimulation (including TLR-ligands/CD40L/IL4). Inhibitors evaluated will include ibrutinib, idelalisib and tamatinib. For in vivo analysis, samples are available from patients treated with ibrutinib or idelalisib, as part of on-going clinical trials co-ordinated via the NCRI HaemOnc CLL and Lymphoma study subgroups.

A third project will be to seek the cell of origin of CLL by Ig gene analysis. In U-CLL, there is increased usage of IGHV1-69 gene, often combined to form stereotypic characteristics of the HCDR3, to suggest selection of the leukemic clones. We have already analysed IGHV1-69/IGHJ6 and IGHV1-69/J3 combinations in normal blood B cells and found that a high proportion have stereotypic patterns similar to those described in U-CLL. Phenotypically the IGHV1-69+ve IgM+ normal B cells are naïve and enriched in CD5+ cells, suggesting a restricted sequence repertoire of the B-cells that may transform in CLL. Our future aim will be to further characterize phenotypically and functionally the potential normal counterparts of CLL cells prior to the putative transforming lesion.

All projects will also be expanded to other tumour entities like Hairy Cell Leukaemia and Splenic Lymphomas and verify potential clinical prognostic significance of the varying BCR features.

Key publications

Coelho V, Krysov S, Steele A, Sanchez Hidalgo M, Johnson PW, Chana PS, Packham G, Stevenson FK, Forconi F. Identification in CLL of circulating intraclonal subgroups with varying B-cell receptor expression and function. BLOOD. 2013, published ahead of print August 16, 2013.

Forconi F, Potter KN, Sozzi E, Henderson I, Cencini E, Rossi D, Bomben R, Gattei V, Gaidano G, Packham G, and Stevenson FK. The IGHV1-69/IGHJ3 recombinations of unmutated CLL are distinct from those of normal B cells. BLOOD. 2012 Mar 1;119(9):2106-9.

Forconi F, Potter KN, Wheatley I, Darzentas N, Sozzi E, Stamatopoulos K, Mockridge CI, Packham G, Stevenson FK. The normal IGHV1-69-derived B-cell repertoire contains stereotypic patterns characteristic of unmutated CLL. BLOOD. 2010 Jan 7;115(1):71-7.

Capitani N, Lucherini OM, Sozzi E, Ferro M, Giommoni N, Finetti F, De Falco G, Cencini E, Raspadori D, Pelicci PG, Lauria F, Forconi F, Baldari CT. Impaired expression of p66Shc, a novel regulator of B-cell survival, in chronic lymphocytic leukemia. BLOOD. 2010 May 6;115(18):3726-36.

Forconi F, Sozzi E, Cencini E, Zaja F, Intermesoli T, Stelitano C, Rigacci L, Gherlinzoni F, Cantaffa R, Baraldi A, Gallamini A, Zaccaria A, Pulsoni A, Gobbi M, Tassi M, Raspadori D, Leoncini L, Rinaldi A, Sabattini E, Bertoni F, Pileri SA, Lauria F. Hairy cell leukemias with unmutated IGHV genes define the minor subset refractory to single-agent cladribine and with more aggressive behavior. BLOOD. 2009 Nov 19;114(21):4696-702.

Forconi F, Sahota SS, Raspadori D, Ippoliti M, Babbage G, Lauria F, Stevenson FK. Hairy cell leukemia: at the crossroad of somatic mutation and isotype switch. BLOOD. 2004 Nov 15;104(10):3312-7. Epub 2004 Jul 29.

PhD Supervision

2008-2011 Elisa Sozzi (PhD) – University of Siena

2011 Anna Sicuranza (PhD) – University of Siena

2012-2016 Annalisa D’Avola – University of Southampton

2013-2016 Giorgia Chiodin – University of Padua, Italy

2015-2019 Sarah Wilmore – University of Southampton

2015-2020 Yohannes Gebreselassie – University of Southampton

2017-present - David Dutton – CRUK Clinical fellow (DM/PhD degree)

2020-2024: iPhD student supervisor (4 years, TBA)

PhD thesis viva-voce examiner

2018 Jul 20th - University of Leeds

2017 Oct 11th - University of Southampton

2016 Nov 24th - University of Liverpool

2014 Dec 18th - King's College London

Research Projects

Please find them on our Research Theme page

Department(s)

Cancer Sciences

Affiliate Department(s)

Cancer Sciences Research group

Chair of the Faculty of Medicine (FoM) Conference, 2019-present

School of Cancer Sciences Operations Board, 2018-present

Cancer Sciences Seminars Series organiser, 2012-2015

Editorial Boards

  • Blood, journal of the American Society of Hematology, Editorial board member (2020 – present)
  • EHA Editorial board Associate reviewer (Clinical Hematology Lymphoid malignancies section) at the EHA Executive Office Learning Center (2015 – present)
  • Clinical Hemorheology and Microcirculation, Editorial board member (2012- present)

Reviewer for major international Haematology journals: Nature Cancer (2019-present), Blood (2011-present), Blood advances (2018 – present), Science Reports (2019 – present), Clinical Cancer Research (2018-present), Haematologica (2000-present), Leukemia (2000-present), Cancer Research (2018-present), Oncotarget (2014-present), British Journal of Haematology (1998-present), Leukemia and Lymphoma (1998-present), Haematological Oncology (2010-present), Molecular Medicine (2015-present).

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Teaching at the University of Southampton

  • Deputy Module Leader  and Clinical Advisor for Cancer in the ELC Module (MEDI 2043), 2019-present
  • Head, Haematology Field (MEDI3048), Research projects - BM5 (A100), BM(EU) (A103) , BM6 (A102) undergraduate degrees, 2012-present
  • Supervisor, Haematology Field (MEDI3048), Research projects - BM5 (A100), BM(EU) (A103) , BM6 (A102) undergraduate degrees, 2012-present
  • Personal Academic Tutor (PAT), 2018-present
  • Educational Supervisor, Southampton University Hospital Trust (Wessex Deanery), 2015-present
  • Supervisor of EU Medical Students at the Haematology Dept, Southampton University Hospital Trust, 2015-present
  • Supervisor of International Fellows at the School of Cancer Sciences, University of Southampton, 2014-present
  • Supervisor for Masters in Medical Sciences, 2019-present

Teaching for non-UK academic organisations since 2011

  • European School of Oncology (ESO) and Ulm University, Germany - Certificate of Competence in Lymphoma (CCL) programme - topic Hairy Cell Leukemia (2013-present)
  • Lecturer (Professore Aggregato) in Haematology University of Siena, Italy (2018-present)
  • Academic Board of the PhD Programme in Medical Sciences and Biotechnology, University of Eastern Piedmont, Novara, Italy (2019-present)
Dr Francesco Forconi
Haematology Oncology Group | School of Cancer Sciences | Faculty of Medicine | University of Southampton | Room CS/B9, MP824 Somers Building, Southampton General Hospital, Tremona Rd, Southampton, SO16 6YD, UK
Tel: +44 (0)23 8120 5780 Email: f.forconi@soton.ac.uk

Room Number: SGH/Somers/MP824

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