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Genomic abnormalities of TP53 define distinct risk groups of paediatric B-cell non-Hodgkin lymphoma

Lookup NU author(s): Dr Alex Newman, Dr Masood Zaka, Dr Peixun Zhou, Alex Blain, Dr Amy Erhorn, Amy Barnard, Dr Rachel CrosslandORCiD, Sarah Wilkinson, Dr Amir EnshaeiORCiD, Fiona Harding, Dr Katrina Wood, Dr Despina Televantou, Dr Simon BomkenORCiD, Dr Christopher Bacon, Professor Vikki Rand

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This work is licensed under a Creative Commons Attribution 4.0 International License (CC BY 4.0).


Abstract

© 2021, The Author(s). Children with B-cell non-Hodgkin lymphoma (B-NHL) have an excellent chance of survival, however, current clinical risk stratification places as many as half of patients in a high-risk group receiving very intensive chemo-immunotherapy. TP53 alterations are associated with adverse outcome in many malignancies; however, whilst common in paediatric B-NHL, their utility as a risk classifier is unknown. We evaluated the clinical significance of TP53 abnormalities (mutations, deletion and/or copy number neutral loss of heterozygosity) in a large UK paediatric B-NHL cohort and determined their impact on survival. TP53 abnormalities were present in 54.7% of cases and were independently associated with a significantly inferior survival compared to those without a TP53 abnormality (PFS 70.0% vs 100%, p < 0.001, OS 78.0% vs 100%, p = 0.002). Moreover, amongst patients clinically defined as high-risk (stage III with high LDH or stage IV), those without a TP53 abnormality have superior survival compared to those with TP53 abnormalities (PFS 100% vs 55.6%, p = 0.005, OS 100% vs 66.7%, p = 0.019). Biallelic TP53 abnormalities were either maintained from the presentation or acquired at progression in all paired diagnosis/progression Burkitt lymphoma cases. TP53 abnormalities thus define clinical risk groups within paediatric B-NHL and offer a novel molecular risk stratifier, allowing more personalised treatment protocols.


Publication metadata

Author(s): Newman AM, Zaka M, Zhou P, Blain AE, Erhorn A, Barnard A, Crossland RE, Wilkinson S, Enshaei A, De Zordi J, Harding F, Taj M, Wood KM, Televantou D, Turner SD, Burke GAA, Harrison CJ, Bomken S, Bacon CM, Rand V

Publication type: Article

Publication status: Published

Journal: Leukemia

Year: 2021

Pages: Epub ahead of print

Online publication date: 21/10/2021

Acceptance date: 29/09/2021

Date deposited: 04/11/2021

ISSN (print): 0887-6924

ISSN (electronic): 1476-5551

Publisher: Springer Nature

URL: https://doi.org/10.1038/s41375-021-01444-6

DOI: 10.1038/s41375-021-01444-6


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Funding

Funder referenceFunder name
12005Bloodwise (Formerly Leukaemia and Lymphoma Research)
MR/S021590/1Medical Research Council (MRC)

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