TP53 mutations in de novo acute myeloid leukemia patients: longitudinal follow-ups show the mutation is stable during disease evolution

The TP53 mutation is frequently detected in acute myeloid leukemia (AML) patients with complex karyotype (CK), but the stability of this mutation during the clinical course remains unclear. In this study, TP53 mutations were identified in 7% of 500 patients with de novo AML and 58.8% of patients wit...

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Main Authors:	Hou, H-A, Chou, W-C, Kuo, Y-Y, Liu, C-Y, Lin, L-I, Tseng, M-H, Chiang, Y-C, Liu, M-C, Liu, C-W, Tang, J-L, Yao, M, Li, C-C, Huang, S-Y, Ko, B-S, Hsu, S-C, Chen, C-Y, Lin, C-T, Wu, S-J, Tsay, W, Chen, Y-C, Tien, H-F
Format:	Online
Language:	English
Published:	Nature Publishing Group 2015
Online Access:	https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4526785/

id	pubmed-4526785
recordtype	oai_dc
spelling	pubmed-45267852015-08-06 TP53 mutations in de novo acute myeloid leukemia patients: longitudinal follow-ups show the mutation is stable during disease evolution Hou, H-A Chou, W-C Kuo, Y-Y Liu, C-Y Lin, L-I Tseng, M-H Chiang, Y-C Liu, M-C Liu, C-W Tang, J-L Yao, M Li, C-C Huang, S-Y Ko, B-S Hsu, S-C Chen, C-Y Lin, C-T Wu, S-J Tsay, W Chen, Y-C Tien, H-F Original Article The TP53 mutation is frequently detected in acute myeloid leukemia (AML) patients with complex karyotype (CK), but the stability of this mutation during the clinical course remains unclear. In this study, TP53 mutations were identified in 7% of 500 patients with de novo AML and 58.8% of patients with CK. TP53 mutations were closely associated with older age, lower white blood cell (WBC) and platelet counts, FAB M6 subtype, unfavorable-risk cytogenetics and CK, but negatively associated with NPM1 mutation, FLT3/ITD and DNMT3A mutation. Multivariate analysis demonstrated that TP53 mutation was an independent poor prognostic factor for overall survival and disease-free survival among the total cohort and the subgroup of patients with CK. A scoring system incorporating TP53 mutation and nine other prognostic factors, including age, WBC counts, cytogenetics and gene mutations, into survival analysis proved to be very useful to stratify AML patients. Sequential study of 420 samples showed that TP53 mutations were stable during AML evolution, whereas the mutation was acquired only in 1 of the 126 TP53 wild-type patients when therapy-related AML originated from different clone emerged. In conclusion, TP53 mutations are associated with distinct clinic-biological features and poor prognosis in de novo AML patients and are rather stable during disease progression. Nature Publishing Group 2015-07 2015-07-31 /pmc/articles/PMC4526785/ /pubmed/26230955 http://dx.doi.org/10.1038/bcj.2015.59 Text en Copyright © 2015 Macmillan Publishers Limited http://creativecommons.org/licenses/by/4.0/ This work is licensed under a Creative Commons Attribution 4.0 International License. The images or other third party material in this article are included in the article's Creative Commons license, unless indicated otherwise in the credit line; if the material is not included under the Creative Commons license, users will need to obtain permission from the license holder to reproduce the material. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/
repository_type	Open Access Journal
institution_category	Foreign Institution
institution	US National Center for Biotechnology Information
building	NCBI PubMed
collection	Online Access
language	English
format	Online
author	Hou, H-A Chou, W-C Kuo, Y-Y Liu, C-Y Lin, L-I Tseng, M-H Chiang, Y-C Liu, M-C Liu, C-W Tang, J-L Yao, M Li, C-C Huang, S-Y Ko, B-S Hsu, S-C Chen, C-Y Lin, C-T Wu, S-J Tsay, W Chen, Y-C Tien, H-F
spellingShingle	Hou, H-A Chou, W-C Kuo, Y-Y Liu, C-Y Lin, L-I Tseng, M-H Chiang, Y-C Liu, M-C Liu, C-W Tang, J-L Yao, M Li, C-C Huang, S-Y Ko, B-S Hsu, S-C Chen, C-Y Lin, C-T Wu, S-J Tsay, W Chen, Y-C Tien, H-F TP53 mutations in de novo acute myeloid leukemia patients: longitudinal follow-ups show the mutation is stable during disease evolution
author_facet	Hou, H-A Chou, W-C Kuo, Y-Y Liu, C-Y Lin, L-I Tseng, M-H Chiang, Y-C Liu, M-C Liu, C-W Tang, J-L Yao, M Li, C-C Huang, S-Y Ko, B-S Hsu, S-C Chen, C-Y Lin, C-T Wu, S-J Tsay, W Chen, Y-C Tien, H-F
author_sort	Hou, H-A
title	TP53 mutations in de novo acute myeloid leukemia patients: longitudinal follow-ups show the mutation is stable during disease evolution
title_short	TP53 mutations in de novo acute myeloid leukemia patients: longitudinal follow-ups show the mutation is stable during disease evolution
title_full	TP53 mutations in de novo acute myeloid leukemia patients: longitudinal follow-ups show the mutation is stable during disease evolution
title_fullStr	TP53 mutations in de novo acute myeloid leukemia patients: longitudinal follow-ups show the mutation is stable during disease evolution
title_full_unstemmed	TP53 mutations in de novo acute myeloid leukemia patients: longitudinal follow-ups show the mutation is stable during disease evolution
title_sort	tp53 mutations in de novo acute myeloid leukemia patients: longitudinal follow-ups show the mutation is stable during disease evolution
description	The TP53 mutation is frequently detected in acute myeloid leukemia (AML) patients with complex karyotype (CK), but the stability of this mutation during the clinical course remains unclear. In this study, TP53 mutations were identified in 7% of 500 patients with de novo AML and 58.8% of patients with CK. TP53 mutations were closely associated with older age, lower white blood cell (WBC) and platelet counts, FAB M6 subtype, unfavorable-risk cytogenetics and CK, but negatively associated with NPM1 mutation, FLT3/ITD and DNMT3A mutation. Multivariate analysis demonstrated that TP53 mutation was an independent poor prognostic factor for overall survival and disease-free survival among the total cohort and the subgroup of patients with CK. A scoring system incorporating TP53 mutation and nine other prognostic factors, including age, WBC counts, cytogenetics and gene mutations, into survival analysis proved to be very useful to stratify AML patients. Sequential study of 420 samples showed that TP53 mutations were stable during AML evolution, whereas the mutation was acquired only in 1 of the 126 TP53 wild-type patients when therapy-related AML originated from different clone emerged. In conclusion, TP53 mutations are associated with distinct clinic-biological features and poor prognosis in de novo AML patients and are rather stable during disease progression.
publisher	Nature Publishing Group
publishDate	2015
url	https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4526785/
_version_	1613256336272785408

TP53 mutations in de novo acute myeloid leukemia patients: longitudinal follow-ups show the mutation is stable during disease evolution

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