Cargando…

伴TP53基因异常急性髓系白血病患者的临床特征及预后分析

OBJECTIVE: To explore the clinical and prognostic values of TP53 gene mutation in patients with acute myeloid leukemia (AML) . METHODS: A retrospective analysis of 265 newly diagnosed AML patients with next-generation sequencing (NGS) data in the Hematology Department of Changhai Hospital from Janua...

Descripción completa

Detalles Bibliográficos
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Editorial office of Chinese Journal of Hematology 2019
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7342383/
https://www.ncbi.nlm.nih.gov/pubmed/31856443
http://dx.doi.org/10.3760/cma.j.issn.0253-2727.2019.11.009
_version_ 1783555467111301120
collection PubMed
description OBJECTIVE: To explore the clinical and prognostic values of TP53 gene mutation in patients with acute myeloid leukemia (AML) . METHODS: A retrospective analysis of 265 newly diagnosed AML patients with next-generation sequencing (NGS) data in the Hematology Department of Changhai Hospital from January 2010 to January 2019 was performed. Mutation analysis was carried out by targeted sequencing technology including 200 hematological malignancy related genes. The association of TP53 mutation with clinical features was analyzed. RESULTS: Alterations in TP53 were found in 20 (7.5%) patients, including 17 case (6.4%) of missense mutations, 2 cases (0.7%) of frame-shift deletion mutations and 1 case (0.4%) of splicing sites mutation. A total of 23 kinds of TP53 mutations were detected, most of them (16, 69.6%) were located in the DNA binding domain of exon 5–8, 4 in the DNA binding domain of exon 3–4, 2 in exon 10 and 1 in splice site, respectively. The median age of patients with TP53 alterations was higher than those without [52 (26–72) years old vs 45 (14–75) years old, P= 0.008]. The frequency of complex karyotypes was higher in patients with TP53 alterations than those without [45.0% (9/20) vs6.1% (15/245) , P<0.001]. Median overall survival (OS) of patients with TP53 alterations was shorter than those without[14.1 (95%CI 6.78–21.42) months vs 31.4 (95%CI 13.20–49.59) months, P=0.029]. The OS of patients treated with “Decitabine + CAG” was superior than that of patients treated with “3 + 7” regimen [30.0 (95%CI 27.35–38.84) months vs 12.5 (95%CI 5.80–19.19) months, P=0.018]. Multivariate analysis indicated that TP53, DNMT3A and USH2A alterations, WBC ≥ 12.45×10(9)/L had negative impacts on OS. CONCLUSION: The frequency of TP53 mutation was 7.5% in our cohort. Most mutations were located in the DNA binding domain. TP53 alterations were strongly associated with older age, complex karyotype and shorter OS. Decitabine-based induction chemotherapy and hematopoietic stem cell transplantation may improve OS, more cases and/or multicenter randomized studies are needed for further confirmation.
format Online
Article
Text
id pubmed-7342383
institution National Center for Biotechnology Information
language English
publishDate 2019
publisher Editorial office of Chinese Journal of Hematology
record_format MEDLINE/PubMed
spelling pubmed-73423832020-07-16 伴TP53基因异常急性髓系白血病患者的临床特征及预后分析 Zhonghua Xue Ye Xue Za Zhi 论著 OBJECTIVE: To explore the clinical and prognostic values of TP53 gene mutation in patients with acute myeloid leukemia (AML) . METHODS: A retrospective analysis of 265 newly diagnosed AML patients with next-generation sequencing (NGS) data in the Hematology Department of Changhai Hospital from January 2010 to January 2019 was performed. Mutation analysis was carried out by targeted sequencing technology including 200 hematological malignancy related genes. The association of TP53 mutation with clinical features was analyzed. RESULTS: Alterations in TP53 were found in 20 (7.5%) patients, including 17 case (6.4%) of missense mutations, 2 cases (0.7%) of frame-shift deletion mutations and 1 case (0.4%) of splicing sites mutation. A total of 23 kinds of TP53 mutations were detected, most of them (16, 69.6%) were located in the DNA binding domain of exon 5–8, 4 in the DNA binding domain of exon 3–4, 2 in exon 10 and 1 in splice site, respectively. The median age of patients with TP53 alterations was higher than those without [52 (26–72) years old vs 45 (14–75) years old, P= 0.008]. The frequency of complex karyotypes was higher in patients with TP53 alterations than those without [45.0% (9/20) vs6.1% (15/245) , P<0.001]. Median overall survival (OS) of patients with TP53 alterations was shorter than those without[14.1 (95%CI 6.78–21.42) months vs 31.4 (95%CI 13.20–49.59) months, P=0.029]. The OS of patients treated with “Decitabine + CAG” was superior than that of patients treated with “3 + 7” regimen [30.0 (95%CI 27.35–38.84) months vs 12.5 (95%CI 5.80–19.19) months, P=0.018]. Multivariate analysis indicated that TP53, DNMT3A and USH2A alterations, WBC ≥ 12.45×10(9)/L had negative impacts on OS. CONCLUSION: The frequency of TP53 mutation was 7.5% in our cohort. Most mutations were located in the DNA binding domain. TP53 alterations were strongly associated with older age, complex karyotype and shorter OS. Decitabine-based induction chemotherapy and hematopoietic stem cell transplantation may improve OS, more cases and/or multicenter randomized studies are needed for further confirmation. Editorial office of Chinese Journal of Hematology 2019-11 /pmc/articles/PMC7342383/ /pubmed/31856443 http://dx.doi.org/10.3760/cma.j.issn.0253-2727.2019.11.009 Text en 2019年版权归中华医学会所有 http://creativecommons.org/licenses/by-nc-sa/3.0/ This work is licensed under a Creative Commons Attribution 3.0 License (CC-BY-NC). The Copyright own by Publisher. Without authorization, shall not reprint, except this publication article, shall not use this publication format design. Unless otherwise stated, all articles published in this journal do not represent the views of the Chinese Medical Association or the editorial board of this journal.
spellingShingle 论著
伴TP53基因异常急性髓系白血病患者的临床特征及预后分析
title 伴TP53基因异常急性髓系白血病患者的临床特征及预后分析
title_full 伴TP53基因异常急性髓系白血病患者的临床特征及预后分析
title_fullStr 伴TP53基因异常急性髓系白血病患者的临床特征及预后分析
title_full_unstemmed 伴TP53基因异常急性髓系白血病患者的临床特征及预后分析
title_short 伴TP53基因异常急性髓系白血病患者的临床特征及预后分析
title_sort 伴tp53基因异常急性髓系白血病患者的临床特征及预后分析
topic 论著
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7342383/
https://www.ncbi.nlm.nih.gov/pubmed/31856443
http://dx.doi.org/10.3760/cma.j.issn.0253-2727.2019.11.009
work_keys_str_mv AT bàntp53jīyīnyìchángjíxìngsuǐxìbáixuèbìnghuànzhědelínchuángtèzhēngjíyùhòufēnxī
AT bàntp53jīyīnyìchángjíxìngsuǐxìbáixuèbìnghuànzhědelínchuángtèzhēngjíyùhòufēnxī
AT bàntp53jīyīnyìchángjíxìngsuǐxìbáixuèbìnghuànzhědelínchuángtèzhēngjíyùhòufēnxī
AT bàntp53jīyīnyìchángjíxìngsuǐxìbáixuèbìnghuànzhědelínchuángtèzhēngjíyùhòufēnxī
AT bàntp53jīyīnyìchángjíxìngsuǐxìbáixuèbìnghuànzhědelínchuángtèzhēngjíyùhòufēnxī
AT bàntp53jīyīnyìchángjíxìngsuǐxìbáixuèbìnghuànzhědelínchuángtèzhēngjíyùhòufēnxī
AT bàntp53jīyīnyìchángjíxìngsuǐxìbáixuèbìnghuànzhědelínchuángtèzhēngjíyùhòufēnxī
AT bàntp53jīyīnyìchángjíxìngsuǐxìbáixuèbìnghuànzhědelínchuángtèzhēngjíyùhòufēnxī
AT bàntp53jīyīnyìchángjíxìngsuǐxìbáixuèbìnghuànzhědelínchuángtèzhēngjíyùhòufēnxī