Professor Sylvie Freeman is an Honorary Consultant Haematologist in the departments of Clinical Immunology, University of Birmingham and Haematology, University Hospital Birmingham. Closely involved in the Birmingham Clinical Immunology Service, she specializes in the immunophenotypic detection of minimal residual disease and leukaemic stems cells in acute myeloid leukaemia.
Professor of ImmunoHaematology, Department of Clinical Immunology, Institute of Immunology and Immunotherapy, College of Medical and Dental Sciences, University of Birmingham.
Honorary Consultant, Department of Haematology, University of Birmingham Hospital NHS Trust
Background and Research focus
Professor Freeman specialises in immunophenotypic diagnosis and monitoring of haematological malignancies with particular interest in acute myeloid leukaemia (AML) and myelodysplasia. AML is an aggressive malignancy of the bone marrow which is derived from a rare population of self-renewing leukemic stem cells (LSCs). The persistence of LSCs even after chemotherapy and radiation treatments strongly correlates with disease relapse.
In collaboration with Prof Craddock / Prof Vyas, Prof Freeman’s group have preliminary data pointing to the potential of tracking LSC populations by flow cytometry (MFC) pre and post allogeneic transplantation to guide immunotherapeutic interventions (LLR funding to investigate this further in the FIGARO RIC transplantation study). This is an extension of her work as a collaborator in a study led by Professors Vyas (Oxford University), Weissmann / Majeti (Stanford University California), and Burnett (Cardiff University) (funded by CIRM/MRC) that is developing novel therapeutic antibodies directed against clinically relevant AML LSCs that preferentially express CD47. Blocking anti-CD47 monoclonal antibodies has proven effective in inducing the phagocytosis of LSCs in models of AML. The programme will aim to develop a GMP grade antibody in readiness for a future human clinical trial.
Prof Freeman has a long standing research focus on developing detection of minimal residual disease in AML by immunophenotyping including novel assays and pretreatment predictors of treatment resistance. The latter (work led by Dr Naeem Khan) include functional flow assays such as the mitochondrial priming assay (BH3 profiling) combined with immunophenotype and another assay that allows simultaneous analysis of LSC immunophenotype, redox state (ROS levels) and cell cycle activity. There is also in development a simple MFC assay that might identify prior to treatment AML patients unlikely to respond to standard intensive chemotherapy by their frequency of stem-cell like blasts in blood.
Over the course of the last 5 years her group have undertaken a number of studies supported by CRUK /NIHR /LLR evaluating AML residual disease monitoring by flow cytometry (MFC-MRD) within the UK MRC / NCRI acute myeloid leukaemia (AML) trials. These have the potential to translate into enhanced risk-stratification. The previous MFC-MRD study of older patients in the AML16 (funded by CRUK TRICC) generated data (Freeman et al JCO 2013) that underpins a strategy for MRD directed therapy in older patients in AML18. The AML16 study and interim analysis of younger patients in AML17 (MRD study funded by NIHR) has also produced interesting preliminary data on the relative benefit of consolidation / maintenance in patients when chemosensitive by MFC-MRD.
These studies will provide independent prognostic information and develop more personalised treatment approaches in AML and high risk myelodysplasia.
Immunophenotypic diagnostics; minimal residual disease; acute myeloid leukaemia; myelodysplasia.
Prof Freeman is a Honorary Consultant Haematologist at the University of Birmingham who has an established track record for characterisation of surface markers in myeloid malignancies/myelopoiesis. She also oversees an immunophenotyping service for largest clinical immunohaematology laboratory in UK. This service is responsible for the development of immunophenotyping and molecular B- and T- cell clonality studies to optimise diagnosis and monitoring of haematological malignancies within the West Midlands region. Dr Freeman is a member of UK National Cancer Research Institute Acute Myeloid Leukaemia Working Party and Co–Investigator in UK NCRI AML trials (AML16/17/18), member of the AML18 TMG. Her research has been supported by the Medical Research Council, Cancer Research UK, Leukaemia Research Fund and National Institute for Health Research. Alongside her research commitments, heavily contributes to teaching postgraduate and medical students. In particular she delivers lectures on the MBChB, BMedSci Clinical Sciences Intercalated and MSc in Clinical Oncology courses. She is also clinically active with outpatient clinics in myelodysplasia and general haematology.
Sylvie D. Freeman, Paul Virgo, Steve Couzens, David Grimwade, Nigel Russell, Robert K. Hills and Alan K. BurnettPrognostic relevance of treatment response measured by flow cytometric residual disease detection in older patients with acute myeloid leukemia J Clin Oncol. 2013 Nov 10;31(32):4123-31.
Cobbold M, De La Peña H, Norris A, Polefrone JM, Qian J, English AM, Cummings KL, Penny S, Turner JE, Cottine J, Abelin JG, Malaker SA, Zarling AL, Huang HW, Goodyear O, Freeman SD, Shabanowitz J, Pratt G, Craddock C, Williams ME, Hunt DF, Engelhard VH. MHC class I-associated phosphopeptides are the targets of memory-like immunity in leukemia. Sci Transl Med. 2013 Sep 18;5(203.
C Craddock, L Quek, N Goardon, S Freeman, S Siddique, M Raghavan, A Aztberger, A Schuh, D Grimwade, A Ivey, P Virgo, R Hills, T McSkeane, J Arrazi, S Knapper, C Brookes, B Davies , A Price , K Wall, M Griffiths, J Cavenagh, R Majeti, I Weissman, A Burnett, P Vyas, Azacitidine fails to eradicate leukemic stem/progenitor cell populations in patients with acute myeloid leukemia and myelodysplasia, Leukemia Apr;27(5):1028-36 2013.
Alan K Burnett, Nigel Russell, Robert K Hills, Jonathan Kell, Sylvie Freeman, Lars Kjeldsen, Ann Hunter, John Yin, Charles Craddock, Inge Hoegh Dufva, Keith Wheatley, Donald Milligan. The Addition of Gemtuzumab Ozogamicin to Induction Chemotherapy Improves Survival in Older Patients with Acute Myeloid Leukaemia. J Clin Oncol. Nov 10;30(32):3924-31 2012.
Clarke M, Dumon S, Ward C, Jäger R, Freeman S, Dawood B, Sheriff L, Lorvellec M, Kralovics R, Frampton J, García P. MYBL2 haploinsufficiency increases susceptibility to age-related haematopoietic neoplasia. Leukemia. Mar;27(3):661-70 2013.
Della Porta MG, Picone C, Pascutto C, Malcovati L, Tamura H, Handa H, Czader M, Freeman S, Vyas P, Porwit A, Saft L, Westers TM, Alhan C, Cali C, Van de Loosdrecht AA, Ogata K. Multicentre validation of a reproducible flow cytometric score for the diagnosis of low-risk myelodysplastic syndromes: results of a European LeukemiaNET study. Haematologica. 2012 Aug;97(8):1209-17.
Jenkins P, Scaife J, Freeman S. Validation of a predictive model that identifies patients at high risk of developing febrile neutropaenia following chemotherapy for breast cancer. Ann Oncol. 2012 Jul;23(7).
Grimwade D, Vyas P, Freeman S. Assessment of Minimal Residual Disease in acute myeloid leukemia. Current Opinion in Oncology 2010 Nov;22(6):656-63. Review.
Goardon N, Nikolousis E, Sternberg A, Chu W, Craddock C, Benson R, DraysonM, Standen G, Vyas P, Freeman S. Reduced CD38 expression on CD34+ cells as a diagnostic test in Myelodysplastic Syndromes. Haematologica 2009 Aug;94(8):1160-3.
Khanim FL, Bradbury CA, Arrazi J, Hayden RE, Rye A, Basu S, Macwhannell A, Sawers A, Griffiths M, Cook M, Freeman S, Nightingale KP, Grimwade D, Falciani F, Turner BM, Bunce CM, Craddock C. Elevated FOSB-expression; a potential marker of valproate sensitivity in AML. Br J Haematol. 2009 Feb 1;144(3):332-341.