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Cytogenetics and molecular genetics

The impact of TP53 mutations and TP53 deletions on survival varies between AML, ALL, MDS and CLL: an analysis of 3307 cases

Abstract

Alterations in TP53 have been described in many cancer types including hematological neoplasms. We aimed at comparing TP53 mutations (mut) and deletions (del) in a large cohort of patients with hematological malignancies (n=3307), including AML (n=858), MDS (n=943), ALL (n=358), CLL (n=1148). Overall, alterations in TP53 were detected in 332/3307 cases (10%). The highest frequency was observed in ALL (total: 19%; mut+del: 6%; mut only: 8%; del only: 5%) and AML (total: 13%; mut+del: 5%; mut only: 7%; del only: 1%), whereas TP53 alterations occurred less frequently in CLL (total: 8%) and MDS (total: 7%). TP53 mutations were significantly more frequent in patients 60 vs <60 years in AML (9% vs 2%, P<0.001) and ALL (12% vs 6%, P<0.001). TP53mut+del had a significant negative impact on overall survival in all entities, whereas differences were observed regarding TP53mut only or TP53del only: TP53mut only impacted survival in AML (36 vs 9 months, P<0.001) and MDS (65 vs 19 months, P<0.001), TP53del only in CLL (not reached vs 64 months, P=0.008) and MDS (65 vs 24 months, P=0.011). As substantial differences between the entities are observed regarding correlation to age and survival, we suggest evaluation of both TP53 deletion and mutation status.

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Acknowledgements

We thank all co-workers at the MLL Munich Leukemia Laboratory for their technical assistance. We thank all physicians for providing and caring for patients as well as collecting the data.

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Correspondence to A Stengel.

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CH, WK and TH declare part ownership of MLL Munich Leukemia Laboratory. AS, MM and AF are employed by MLL Munich Leukemia Laboratory.

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Stengel, A., Kern, W., Haferlach, T. et al. The impact of TP53 mutations and TP53 deletions on survival varies between AML, ALL, MDS and CLL: an analysis of 3307 cases. Leukemia 31, 705–711 (2017). https://doi.org/10.1038/leu.2016.263

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