Paediatric Burkitt lymphoma patient-derived xenografts capture disease characteristics over time and are a model for therapy

Sorcha Forde; Jamie D. Matthews; Leila Jahangiri; Liam C. Lee; Nina Prokoph; Tim I.M. Malcolm; Olivier T. Giger; Natalie Bell; Helen Blair; Aengus O'Marcaigh; Owen Smith; Lukas Kenner; Simon Bomken; Gladstone A.A. Burke; Suzanne D. Turner

doi:10.1111/bjh.17043

Paediatric Burkitt lymphoma patient-derived xenografts capture disease characteristics over time and are a model for therapy

Sorcha Forde, Jamie D. Matthews, Leila Jahangiri, Liam C. Lee, Nina Prokoph, Tim I.M. Malcolm, Olivier T. Giger, Natalie Bell, Helen Blair, Aengus O'Marcaigh, Owen Smith, Lukas Kenner, Simon Bomken, Gladstone A.A. Burke, Suzanne D. Turner^*

^*Corresponding author for this work

Cancer and Genomic Sciences

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Abstract

Burkitt lymphoma (BL) accounts for almost two-thirds of all B-cell non-Hodgkin lymphoma (B-NHL) in children and adolescents and is characterised by a MYC translocation and rapid cell turnover. Intensive chemotherapeutic regimens have been developed in recent decades, including the lymphomes malins B (LMB) protocol, which have resulted in a survival rate in excess of 90%. Recent clinical trials have focused on immunochemotherapy, with the addition of rituximab to chemotherapeutic backbones, showing encouraging results. Despite these advances, relapse and refractory disease occurs in up to 10% of patients and salvage options for these carry a dismal prognosis. Efforts to better understand the molecular and functional characteristics driving relapse and refractory disease may help improve this prognosis. This study has established a paediatric BL patient-derived xenograft (PDX) resource which captures and maintains tumour heterogeneity, may be used to better characterise tumours and identify cell populations responsible for therapy resistance.

Original language	English
Pages (from-to)	354-365
Number of pages	12
Journal	British Journal of Haematology
Volume	192
Issue number	2
Early online date	3 Sept 2020
DOIs	https://doi.org/10.1111/bjh.17043
Publication status	Published - Jan 2021

Bibliographical note

Funding Information:
We are grateful to Dave, Nic, Brenda and Matt for their support, courage and determination to put an end to childhood cancer in memory of Alex. SF, JDM, GAAB and SDT are supported with funding from the Alex Hulme Foundation. We thank the Cambridge NIHR BRC Cell Phenotyping Hub, Addenbrooke’s Hospital, Cambridge; Central Biomedical Services (CBS), Addenbrooke’s Hospital, Cambridge; Haematopathology and Oncology Diagnostic Service (HODS) Lab, Addenbrooke’s Hospital, Cambridge; and the Histology Lab, Department of Pathology, University of Cambridge. We are also extremely grateful to all the children and their parents who donated their tumour tissues for this study.

Publisher Copyright:
© 2020 The Authors. British Journal of Haematology published by British Society for Haematology and John Wiley & Sons Ltd

Keywords

B-cell lymphoma
Burkitt lymphoma
murine cancer models
patient derived xenograft
relapse

ASJC Scopus subject areas

Hematology

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

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Cite this

Forde, S., Matthews, J. D., Jahangiri, L., Lee, L. C., Prokoph, N., Malcolm, T. I. M., Giger, O. T., Bell, N., Blair, H., O'Marcaigh, A., Smith, O., Kenner, L., Bomken, S., Burke, G. A. A., & Turner, S. D. (2021). Paediatric Burkitt lymphoma patient-derived xenografts capture disease characteristics over time and are a model for therapy. British Journal of Haematology, 192(2), 354-365. https://doi.org/10.1111/bjh.17043

@article{c0165d570e5a4e80a51b63bdd59a7cc0,

title = "Paediatric Burkitt lymphoma patient-derived xenografts capture disease characteristics over time and are a model for therapy",

abstract = "Burkitt lymphoma (BL) accounts for almost two-thirds of all B-cell non-Hodgkin lymphoma (B-NHL) in children and adolescents and is characterised by a MYC translocation and rapid cell turnover. Intensive chemotherapeutic regimens have been developed in recent decades, including the lymphomes malins B (LMB) protocol, which have resulted in a survival rate in excess of 90%. Recent clinical trials have focused on immunochemotherapy, with the addition of rituximab to chemotherapeutic backbones, showing encouraging results. Despite these advances, relapse and refractory disease occurs in up to 10% of patients and salvage options for these carry a dismal prognosis. Efforts to better understand the molecular and functional characteristics driving relapse and refractory disease may help improve this prognosis. This study has established a paediatric BL patient-derived xenograft (PDX) resource which captures and maintains tumour heterogeneity, may be used to better characterise tumours and identify cell populations responsible for therapy resistance.",

keywords = "B-cell lymphoma, Burkitt lymphoma, murine cancer models, patient derived xenograft, relapse",

author = "Sorcha Forde and Matthews, {Jamie D.} and Leila Jahangiri and Lee, {Liam C.} and Nina Prokoph and Malcolm, {Tim I.M.} and Giger, {Olivier T.} and Natalie Bell and Helen Blair and Aengus O'Marcaigh and Owen Smith and Lukas Kenner and Simon Bomken and Burke, {Gladstone A.A.} and Turner, {Suzanne D.}",

note = "Funding Information: We are grateful to Dave, Nic, Brenda and Matt for their support, courage and determination to put an end to childhood cancer in memory of Alex. SF, JDM, GAAB and SDT are supported with funding from the Alex Hulme Foundation. We thank the Cambridge NIHR BRC Cell Phenotyping Hub, Addenbrooke{\textquoteright}s Hospital, Cambridge; Central Biomedical Services (CBS), Addenbrooke{\textquoteright}s Hospital, Cambridge; Haematopathology and Oncology Diagnostic Service (HODS) Lab, Addenbrooke{\textquoteright}s Hospital, Cambridge; and the Histology Lab, Department of Pathology, University of Cambridge. We are also extremely grateful to all the children and their parents who donated their tumour tissues for this study. Publisher Copyright: {\textcopyright} 2020 The Authors. British Journal of Haematology published by British Society for Haematology and John Wiley & Sons Ltd",

year = "2021",

month = jan,

doi = "10.1111/bjh.17043",

language = "English",

volume = "192",

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Forde, S, Matthews, JD, Jahangiri, L, Lee, LC, Prokoph, N, Malcolm, TIM, Giger, OT, Bell, N, Blair, H, O'Marcaigh, A, Smith, O, Kenner, L, Bomken, S, Burke, GAA & Turner, SD 2021, 'Paediatric Burkitt lymphoma patient-derived xenografts capture disease characteristics over time and are a model for therapy', British Journal of Haematology, vol. 192, no. 2, pp. 354-365. https://doi.org/10.1111/bjh.17043

TY - JOUR

T1 - Paediatric Burkitt lymphoma patient-derived xenografts capture disease characteristics over time and are a model for therapy

AU - Forde, Sorcha

AU - Matthews, Jamie D.

AU - Jahangiri, Leila

AU - Lee, Liam C.

AU - Prokoph, Nina

AU - Malcolm, Tim I.M.

AU - Giger, Olivier T.

AU - Bell, Natalie

AU - Blair, Helen

AU - O'Marcaigh, Aengus

AU - Smith, Owen

AU - Kenner, Lukas

AU - Bomken, Simon

AU - Burke, Gladstone A.A.

AU - Turner, Suzanne D.

N1 - Funding Information: We are grateful to Dave, Nic, Brenda and Matt for their support, courage and determination to put an end to childhood cancer in memory of Alex. SF, JDM, GAAB and SDT are supported with funding from the Alex Hulme Foundation. We thank the Cambridge NIHR BRC Cell Phenotyping Hub, Addenbrooke’s Hospital, Cambridge; Central Biomedical Services (CBS), Addenbrooke’s Hospital, Cambridge; Haematopathology and Oncology Diagnostic Service (HODS) Lab, Addenbrooke’s Hospital, Cambridge; and the Histology Lab, Department of Pathology, University of Cambridge. We are also extremely grateful to all the children and their parents who donated their tumour tissues for this study. Publisher Copyright: © 2020 The Authors. British Journal of Haematology published by British Society for Haematology and John Wiley & Sons Ltd

PY - 2021/1

Y1 - 2021/1

N2 - Burkitt lymphoma (BL) accounts for almost two-thirds of all B-cell non-Hodgkin lymphoma (B-NHL) in children and adolescents and is characterised by a MYC translocation and rapid cell turnover. Intensive chemotherapeutic regimens have been developed in recent decades, including the lymphomes malins B (LMB) protocol, which have resulted in a survival rate in excess of 90%. Recent clinical trials have focused on immunochemotherapy, with the addition of rituximab to chemotherapeutic backbones, showing encouraging results. Despite these advances, relapse and refractory disease occurs in up to 10% of patients and salvage options for these carry a dismal prognosis. Efforts to better understand the molecular and functional characteristics driving relapse and refractory disease may help improve this prognosis. This study has established a paediatric BL patient-derived xenograft (PDX) resource which captures and maintains tumour heterogeneity, may be used to better characterise tumours and identify cell populations responsible for therapy resistance.

AB - Burkitt lymphoma (BL) accounts for almost two-thirds of all B-cell non-Hodgkin lymphoma (B-NHL) in children and adolescents and is characterised by a MYC translocation and rapid cell turnover. Intensive chemotherapeutic regimens have been developed in recent decades, including the lymphomes malins B (LMB) protocol, which have resulted in a survival rate in excess of 90%. Recent clinical trials have focused on immunochemotherapy, with the addition of rituximab to chemotherapeutic backbones, showing encouraging results. Despite these advances, relapse and refractory disease occurs in up to 10% of patients and salvage options for these carry a dismal prognosis. Efforts to better understand the molecular and functional characteristics driving relapse and refractory disease may help improve this prognosis. This study has established a paediatric BL patient-derived xenograft (PDX) resource which captures and maintains tumour heterogeneity, may be used to better characterise tumours and identify cell populations responsible for therapy resistance.

KW - B-cell lymphoma

KW - Burkitt lymphoma

KW - murine cancer models

KW - patient derived xenograft

KW - relapse

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DO - 10.1111/bjh.17043

M3 - Article

C2 - 32880915

AN - SCOPUS:85090125689

SN - 0007-1048

VL - 192

SP - 354

EP - 365

JO - British Journal of Haematology

JF - British Journal of Haematology

IS - 2

ER -

Paediatric Burkitt lymphoma patient-derived xenografts capture disease characteristics over time and are a model for therapy

Abstract

Bibliographical note

Keywords

ASJC Scopus subject areas

UN SDGs

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