Staff Profile

Roles and Responsibilities

I am a Clinician Scientist and Honorary Consultant in Paediatric Oncology, providing a clinical service for young people with leukaemia or lymphoma at the Great North Children's Hospital, Newcastle upon Tyne.

Qualifications

• 1994 MD, Katholieke Universiteit Leuven, Belgium
• 2000 CCT in Paediatrics, Vrije Universiteit Brussels, Belgium
• 2000 Full and specialist registration in Paediatrics (GMC registration number 4452924)
• 2008 PhD, Queen Mary University of London, England
• 2013 Fellow of the Royal College of Paediatrics and Child Health (FRCPCH)

Previous Positions

• 1995-1996 Clinique Baron Lambert, Brussels, Belgium, Specialist Registrar in Paediatrics
• 1996-1997 Universitair Ziekenhuis Brussel, Belgium, Specialist Registrar in Paediatrics
• 1997-1998 Great Ormond Street Hospital for Sick Children, London, Specialist Registrar in Paediatrics and Paediatric Haematology & Oncology
• 1998-2000 Universitair Ziekenhuis Brussel, Belgium, Specialist Registrar in Paediatrics and Paediatric Haematology & Oncology
• 2000-2001 Harley Street Clinic, London, Resident Medical Officer in Paediatrics
• 2001-2006 Royal London Hospital & Queen Mary University of London, Clinical Research Fellow in Paediatric Oncology and PhD student
• 2006-2007 University College Hospital, London, Clinical Research Fellow in Paediatric Oncology
• 2007-2013 Royal Marsden Hospital & Institute of Cancer Research, Postdoctoral Fellow in Paediatric Oncology

Memberships

• NCRI Leukaemia Study Group
• NCRI TYA CSG - Biological Studies Subgroup
• IBFM Childhood Leukaemia Study Group - Resistant Disease Committee
• International Leukaemia Tumour Board (iLTB)
• Hem-iSmart Steering Committee
• ITCC Hema Committee
• NIHR CRN CYP TYA Subspecialty Research Lead
• Childhood Leukaemia Research UK
• SIOPE
• CCLG
• EHA
• SOHO

Languages

Dutch, English, French

"Improving outcomes for patients with drug resistant T-cell haematological malignancies."

T-cell acute lymphoblastic leukaemia (T-ALL) is diagnosed in 90 children and teenagers living in the United Kingdom each year. Most of these patients can expect long-term survival with currently available treatment protocols.

The outcome for patients with recurrent or refractory (drug resistant) T-ALL however is unfavourable and this patient group represents a clinical unmet need.

My research group is based in the Wolfson Childhood Cancer Research Centre (WCCRC) at the Newcastle University Centre for Cancer. Our aim is to understand the biology underlying treatment resistant T-lineage haematological malignancies and use this knowledge to improve outcomes for affected children and adults. Our research pertains to T-ALL, T-LBL (lymphoblastic lymphoma) and PTCL (peripheral T cell lymphoma).

The infrastructure at Newcastle University and Great North Children’s Hospital provides a wide range of state-of-the-art services to allow us to interrogate the biology of T-lineage derived malignancies and translate this knowledge into delivering improved therapies in early and late phase clinical trials.

Current research projects at the Wolfson Childhood Cancer Research Centre:

Aberrant activation of developmental pathways frequently underlie the development of cancer. Using an shRNA screen against components of the pre T Cell Receptor (preTCR) pathway, we have identified a critical role for the signalling molecule LCK in proliferation of human T-ALL in mouse models. Excitingly, glucocorticoid resistance in T-ALL cells could be reversed when combining inhibition of LCK with dexamethasone. Inhibition of LCK can be effectively achieved using the second generation tyrosine kinase inhibitor dasatinib, which is already in use for the treatment of BCR-ABL1 positive ALL. We are currently working to understand the mechanism underlying the reversal of drug resistance, as well as identify response biomarkers, with the aim to include this novel therapy in early phase trials. The combination of dexamethasone and dasatinib will be tested in the early phase trial platform HEM-iSMART.  

The initial phase of clinical treatment for patients with T-ALL consists of a four-drug induction regimen containing dexamethasone, vincristine, asparaginase and daunorubicin (VXLD). Response to this induction treatment, as measured by real-time genomic PCR, is predictive for outcome. Understanding mechanisms that provide resistance against this induction regimen has the potential to improve outcomes. We are currently applying a functional genomic screen, using CRISPR/Cas9 technology, to unravel mechanisms of resistance to VXLD treatment in vitro and in vivo.

Philadelphia-like activating kinase mutations are increasingly recognised in B and T-lineage ALL. These patients often demonstrate a poor response to induction therapy and this is reflected in an increased relapse rate. Emerging evidence suggests that these patients benefit from additional tyrosine kinase inhibitor therapy. In order to optimise clinical management, we are undertaking detailed characterisation of these leukaemias integrating genetic and drug response profiling.

Current TTeam members

Dr Alistair Poll postdoctoral researcher

Mr Mankaran Singh NUCancer CRUK PhD student

Previous members

Dr Melanie Beckett - Institute of Cancer Research 

Dr Yuzhe Shi - MSK Cancer Center, USA

Dr Anja Krippner-Heidenreich - Prinses Maxima Centrum, The Netherlands 

UG and MRes students

Collaborations

Professor Julie Irving

Professor Christine Harrison, Professor Anthony Moorman, Dr Claire Schwab (LCRG)

Dr Lisa Russell and Dr Simon Bomken

Dr Gavin Cuthbert, Centre for Life, Newcastle University

Professor Pieter Van Vlierberghe, Ghent University, Belgium

Prof Jean Pierre Bourquin, Dr Beat Bornhauser, Zurich

Dr Jun J Yang, St Jude Children's Research Hospital, Memphis 

Funders

NU

NECCR

JGWP

AMR

CwC

Chinese Government

Team Lewis Trust

I supervise undergraduate, master and PhD students at the Wolfson Childhood Cancer Research Centre, and provide bedside clinical teaching to medical students at the Great North Children's Hospital.

Current students

• Mr Mankaran Singh - PhD student
• Mr Ozcan Gulbey - PhD student (second supervisor)
• Ms Hannah Elkatkat - MRes student
  

Previous students

PhD

• Dr Yuzhe Shi
• Dr Melanie Beckett

UG

• Anna Wong
• Beth Poole
• Rickard Phillips

MRes

• Anukrati Nigam
• Edward Hayter
• Andrew Cairns
• Nicole Cripps
• Khaireen Idzham
• Beth Poole
• Deborah Adekanmbi
• Melissa Lee

MSc

• Melody Yu

I have contributed a chapter titled "The biology of childhood leukaemia" for the 2nd edition of the Oxford specialist handbook in Paediatric Haematology & Oncology.

• Shi Y, Beckett MC, Blair HJ, Tirtakusuma R, Nakjang S, Enshaei A, Halsey C, Vormoor J, Heidenreich O, Krippner-Heidenreich A, van Delft FW. Phase II-like murine trial identifies synergy between dexamethasone and dasatinib in T-cell acute lymphoblastic leukemia. Haematologica 2021, 106(4), 1056-1066.
• Matthijssens F, Sharma ND, Nysus M, Nickl CK, Kang H, Perez DR, Lintermans B, Van Loocke W, Roels J, Peirs S, Demoen L, Pieters T, Reunes L, Lammens T, De Moerloose B, Van Nieuwerburgh F, Deforce DL, Cheung LC, Kotecha RS, Risseeuw MDP, Van Calenbergh S, Takarada T, Yoneda Y, Van Delft FW, Lock RB, Merkley SD, Chigaev A, Sklar LA, Mullighan CG, Loh ML, Winter SS, Hunger SP, Goossens S, Castillo EF, Ornatowski W, Van Vlierberghe P, Matlawska-Wasowska K. RUNX2 regulates leukemic cell metabolism and chemotaxis in high-risk T cell acute lymphoblastic leukemia. Journal of Clinical Investigation 2021, 131(6), 141566.
• Mansur M, Furness CL, Enshaei A, Nakjang S, Alpar D, Colman SM, Minto L, Irving J, Poole BV, Noronha LP, Savola S, Iqbal S, Gribben J, Pombo-de-Oliveira MS, Ford TM, Greaves M, van Delft F. The genomic landscape of teenage and young adult T-cell acute lymphoblastic leukemia. Cancer Medicine 2021, 10(14), 4864-4873.
• Moorman AV, Schwab C, Winterman E, Hancock J, Castleton A, Cummins M, Gibson B, Goulden N, Kearns P, James B, Kirkwood AA, Lancaster D, Madi M, McMillan A, Motwani J, Norton A, O'Marcaigh A, Patrick K, Bhatnagar N, Qureshi A, Richardson D, Stokley S, Taylor G, van Delft FW, Moppett J, Harrison CJ, Samarasinghe S, Vora A. Adjuvant tyrosine kinase inhibitor therapy improves outcome for children and adolescents with acute lymphoblastic leukaemia who have an ABL-class fusion. British Journal of Haematology 2020, 191(5), 844-851.
• Doan M, Case M, Masic D, Hennig H, McQuin C, Caicedo J, Singh S, Goodman A, Wolkenhauer O, Summers H, Jamieson D, van Delft FW, Filby A, Carpenter A, Rees P, Irving J. Label-Free Leukemia Monitoring by Computer Vision. Cytometry A 2020, 97(4), 407-414.
• Panagiotopoulou N, van Delft FW, Stewart JA. Fertility preservation knowledge, attitudes and intentions among children by proxy and adolescents with cancer. Reproductive BioMedicine Online 2019, 39(5), 802-808.
• Herd F, Miller T, van Delft FW, Gabra HO. The peripheral portacath provides safe and convenient venous access in pediatric and adolescent patients. Journal of Pediatric Surgery 2019, 54(7), 1449-1452.
• Furness CL, Mansur MB, Weston VJ, Ermini L, van Delft FW, Jenkinson S, Gale R, Harrison CJ, Pombo-de-Oliveira MS, Sanchez-Martin M, Ferrando AA, Kearns P, Titley I, Ford AM, Potter NE, Greaves M. The subclonal complexity of STIL-TAL1+ T-cell acute lymphoblastic leukaemia. Leukemia 2018, 32, 1984-1993.
• Musgrave KM, van Delft FW, Avery PJ, Clack RM, Chalmers EA, Qureshi A, Vora AJ, Biss TT. Cerebral sinovenous thrombosis in children and young adults with acute lymphoblastic leukaemia – a cohort study from the United Kingdom. British Journal of Haematology 2017, 179(4), 667-669.
• Panagiotopoulou N, van Delft FW, Hale JP, Stewart JA. Fertility Preservation Care for Children and Adolescents with Cancer: An Inquiry to Quantify Professionals' Barriers. Journal of Adolescent and Young Adult Oncology 2017, 6(3), 422-428.
• Forster VJ, van Delft FW, Baird SF, Mair S, Skinner R, Halsey C. Reply: Methotrexate neurotoxicity due to drug interactions: an inadequate folinic acid effect. Cancer Chemotherapy and Pharmacology 2017, 79(4), 841-842.
• Forster VJ, van Delft FW, Baird SF, Mair S, Skinner R, Halsey C. Drug interactions may be important risk factors for methotrexate neurotoxicity, particularly in pediatric leukemia patients. Cancer Chemotherapy and Pharmacology 2016, 78(5), 1093-1096.
• Alpar D, Wren D, Ermini L, Mansur MB, van Delft FW, Bateman M, Titley I, Kearney L, Szczepanski T, Gonzalez D, Ford AM, Potter NE, Greaves M. Clonal origins of ETV6-RUNX1⁺ acute lymphoblastic leukemia: studies in monozygotic twins. Leukemia 2015, 29(4), 839-846.
• Tawana K, Wang J, Renneville A, Bodor C, Hills R, Loveday C, Savic A, van Delft FW, Treleaven J, Georgiades P, Uglow E, Asou N, Uike N, Debeljak M, Jazbec J, Ancliff P, Gale R, Thomas X, Mialou V, Dohner K, Bullinger L, Mueller B, Pabst T, Stelljes M, Schlegelberger B, Wozniak E, Iqbal S, Okosun J, Araf S, Frank AK, Lauridsen FB, Porse B, Nerlov C, Owen C, Dokal I, Gribben J, Smith M, Preudhomme C, Chelala C, Cavenagh J, Fitzgibbon J. Disease evolution and outcomes in familial AML with germline CEBPA mutations. Blood 2015, 126(10), 1214-1223.
• Mansur MB, van Delft FW, Colman SM, Furness CL, Gibson J, Emerenciano M, Kempski H, Clappier E, Cave H, Soulier J, Pombo-de-Oliveira MS, Greaves M, Ford AM. Distinctive genotypes in infants with T-cell acute lymphoblastic leukaemia. British Journal of Haematology 2015, 171(4), 574-584.
• Piccirillo SGM, Colman S, Potter NE, van Delft FW, Lillis S, Carnicer M-J, Kearney L, Watts C, Greaves M. Genetic and Functional Diversity of Propagating Cells in Glioblastoma. Stem Cell Reports 2015, 4(1), 7-15.
• Ford AM, Mansur MB, Furness CL, van Delft FW, Okamura J, Suzuki T, Kobayashi H, Kaneko Y, Greaves M. Protracted dormancy of pre-leukemic stem cells. Leukemia 2015, 29(11), 2202-2207.
• Slamova L, Starkova J, Fronkova E, Zaliova M, Reznickova L, van Delft FW, Vodickova E, Volejnikova J, Zemanova Z, Polgarova K, Cario G, Figueroa M, Kalina T, Fiser K, Bourquin JP, Bornhauser B, Dworzak M, Zuna J, Trka J, Stary J, Hrusak O, Mejstrikova E. CD2-positive B-cell precursor acute lymphoblastic leukemia with an early switch to the monocytic lineage. Leukemia 2014, 28(3), 609-620.
• Musgrave KM, van Delft FW, Clack RM, Chalmers EA, Vora AJ, Biss TT. Cerebral Venous Thrombosis As a Complication of Treatment for Acute Lymphoblastic Leukaemia in Children and Young Adults. In: 56th ASH Annual Meeting and Exposition. 2014, San Francisco, CA, USA: American Society of Hematology.
• Alpar D, Wren D, Mansur MB, Potter NE, van Delft FW, Bateman CM, Kearney L, Szczepanski T, de Castro DG, Ford AM, Greaves M. IDENTIFYING THE DEVELOPMENTAL LEVEL OF LEUKEMIA INITIATION IN ETV6-RUNX1+ACUTE LYMPHOBLASTIC LEUKEMIA BY STUDYING MONOZYGOTIC TWINS. In: 19th Congress of the European Hematology Association. 2014, Milan, Italy: Ferrata Storti Foundation.
• Papaemmanuil E, Rapado I, Li YL, Potter NE, Wedge DC, Tubio J, Alexandrov LB, Van Loo P, Cooke SL, Marshall J, Martincorena I, Hinton J, Gundem G, van Delft FW, Nik-Zainal S, Jones DR, Ramakrishna M, Titley I, Stebbings L, Leroy C, Menzies A, Gamble J, Robinson B, Mudie L, Raine K, O'Meara S, Teague JW, Butler AP, Cazzaniga G, Biondi A, Zuna J, Kempski H, Muschen M, Ford AM, Stratton MR, Greaves M, Campbell PJ. RAG-mediated recombination is the predominant driver of oncogenic rearrangement in ETV6-RUNX1 acute lymphoblastic leukemia. Nature Genetics 2014, 46(2), 116-125.
• Furness CL, Mansur MB, Weston VJ, Jenkinson S, van Delft FW, Kearney L, Titley I, Ford AM, Gale RE, Kearns PR, Ferrando AA, Harrison CJ, Potter NE, Greaves M. The Sub-Clonal Complexity of STIL-TAL1 T-ALL. In: 56th ASH Annual Meeting and Exposition. 2014, San Francisco: American Society of Hematology.
• van Delft FW, Mansur MB, Furness C, Minto L, Irving J, Iqbal S, Noronha E, Colman S, Gribben J, Pombo-de-Oliviera M, Greaves M. Genetics of teenage and young adult t-cell acute lymphoblastic leukaemia. In: BRITISH JOURNAL OF HAEMATOLOGY. 2013, 111 RIVER ST, HOBOKEN 07030-5774, NJ USA: WILEY-BLACKWELL.
• Dunne J, Mannari D, Farzaneh T, Gessner A, van Delft FW, Heidenreich O, Young BD, Gascoyne DM. AML1/ETO and POU4F1 synergy drives B-lymphoid gene expression typical of t(8;21) acute myeloid leukemia. Leukemia 2012, 26(5), 1131-1135.
• van Delft FW, Horsley S, Colman S, Anderson K, Bateman C, Kempski H, Zuna J, Eckert C, Saha V, Kearney L, Ford A, Greaves M. Clonal origins of relapse in ETV6-RUNX1 acute lymphoblastic leukemia. Blood 2011, 117(23), 6247-6254.
• Cazzaniga G, van Delft FW, Lo Nigro L, Ford AM, Score J, Iacobucci I, Mirabile E, Taj M, Colman SM, Biondi A, Greaves M. Developmental origins and impact of BCR-ABL1 fusion and IKZF1 deletions in monozygotic twins with Ph⁺ acute lymphoblastic leukaemia. Blood 2011, 118(20), 5559-5564.
• Anderson K, Lutz C, van Delft FW, Bateman CM, Guo YP, Colman SM, Kempski H, Moorman AV, Titley I, Swansbury J, Kearney L, Enver T, Greaves M. Genetic variegation of clonal architecture and propagating cells in leukaemia. Nature 2011, 469(7330), 356-361.
• van der Weyden L, Giotopoulos G, Rust AG, Matheson LS, van Delft FW, Kong J, Corcoran AE, Greaves MF, Mullighan CG, Huntly BJ, Adams DJ. Modeling the evolution of ETV6-RUNX1-induced B-cell precursor acute lymphoblastic leukemia in mice. Blood 2011, 118(4), 1041-1051.
• Mansur MB, Ford AM, van Delft FW, Gonzalez D, Emerenciano M, Maia RC, Greaves M, Pombo-de-Oliveira MS. Occurrence of identical NOTCH1 mutation in non-twinned sisters with T-cell acute lymphoblastic leukemia. Leukemia 2011, 25(8), 1368-1370.
• Patel N, Krishnan S, Offman MN, Krol M, Moss CX, Leighton C, van Delft FW, Holland M, Liu J, Alexander S, Dempsey C, Ariffin H, Essink M, Eden TO, Watts C, Bates PA, Saha V. A dyad of lymphoblastic lysosomal cysteine proteases degrades the antileukemic drug L-asparaginase. Journal of Clinical Investigation 2009, 119(7), 1964-1973.
• Isoda T, Ford AM, Tomizawa D, van Delft FW, De Castro DG, Mitsuiki N, Score J, Taki T, Morio T, Takagi M, Saji H, Greaves M, Mizutani S. Immunologically silent cancer clone transmission from mother to offspring. Proceedings of the National Academy of Sciences 2009, 106(42), 17882-17885.
• Strefford JC, Worley H, Barber K, Wright S, Stewart ARM, Robinson HM, Bettney G, van Delft FW, Atherton MG, Davies T, Griffiths M, Hing S, Ross FM, Talley P, Saha V, Moorman AV, Harrison CJ. Genome complexity in acute lymphoblastic leukemia is revealed by array-based comparative genomic hybridization. Oncogene 2007, 26(29), 4306-4318.
• Strefford JC, van Delft FW, Robinson HM, Worley H, Yiannikouris O, Selzer R, Richmond T, Hann I, Bellotti T, Raghavan M, Young BD, Saha V, Harrison CJ. Complex genomic alterations and gene expression in acute lymphoblastic leukemia with intrachromosomal amplification of chromosome 21. Proceedings of the National Academy of Sciences of the United States of America 2006, 103(21), 8167-8172.
• van Delft FW, Bellotti T, Luo Z, Jones LK, Patel N, Yiannikouris O, Hill AS, Hubank M, Kempski H, Fletcher D, Chaplin T, Foot N, Young BD, Hann IM, Gammerman A, Saha V. Prospective gene expression analysis accurately subtypes acute leukaemia in children and establishes a commonality between hyperdiploidy and t(12;21) in acute lymphoblastic leukaemia. British Journal of Haematology 2005, 130(1), 26-35.
• Bellotti T, Luo Z, Gammerman A, Van Delft FW, Saha V. Qualified predictions for microarray and proteomics pattern diagnostics with confidence machines. International Journal of Neural Systems 2005, 15(4), 247-258.
• van Delft FW, Saha V. Molecular Techniques to Improve Outcome in Childhood ALL. In: Goulden, N.J., Steward, C.G, ed. Pediatric Hematology: Methods and Protocols. Totowa, N.J: Humana Press, 2004, pp.111-122.
• van Delft FW, Jones LK. Oligonucleotide Microarray Analysis of Gene Expression in Leukemia. In: Goulden, N.J.,Steward, C.G, ed. Pediatric Hematology: Methods and Protocols. Totowa, N.J: Humana Press, 2004, pp.183-196.
• Jones LK, Neat M, van Delft FW, Mitchell MP, Adamaki M, Stoneham SJ, Patel N, Saha V. Cryptic rearrangement involving MLL and AF10 occurring in utero. Leukemia 2003, 17(8), 1667-1669.
• Van Delft F, Chua Y, Foy D, Pritchard J. 12000 miles for parental reassurance. Lancet 1998, 352(9134), 1122.