期刊
LEUKEMIA
卷 36, 期 3, 页码 781-789出版社
SPRINGERNATURE
DOI: 10.1038/s41375-021-01444-6
关键词
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资金
- Blood Cancer UK Senior Bennett Fellowship [12005]
- Newcastle upon Tyne Hospitals NHS Charity, North East Promenaders Against Cancer (NEPAC)
- JGW Patterson Foundation
- Little Princess Trust
- North of England Children's Cancer Research Fund (NECCR)
- Hannah Bloom Charitable Trust
- Cancer Research North East
- National Institute for Health Research (NIHR) Newcastle In Vitro Diagnostics Co-operative
- MRC/EPSRC Newcastle Molecular Pathology Node
- MRC Clinician Scientist Fellowship [MR/S021590/1]
- Cancer Research UK
- Good Will Cause
Research shows that TP53 gene abnormalities are associated with inferior survival rates in children with B-cell non-Hodgkin lymphoma, especially in high-risk patients. These findings provide a novel molecular risk stratifier for more personalized treatment protocols.
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.
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