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IDH不同突变亚型及伴发基因突变对急性髓系白血病患者的预后意义

OBJECTIVE: To investigate the prognostic significance of different IDH mutations and accompanying gene mutations in patients with non-M(3) acute myeloid leukemia (AML). METHODS: Second-generation sequencing was performed to detect the mutations of 22 genes in 389 patients with AML in the First Affil...

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Formato: Online Artículo Texto
Lenguaje:English
Publicado: Editorial office of Chinese Journal of Hematology 2021
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Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7957250/
https://www.ncbi.nlm.nih.gov/pubmed/33677867
http://dx.doi.org/10.3760/cma.j.issn.0253-2727.2021.01.008
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description OBJECTIVE: To investigate the prognostic significance of different IDH mutations and accompanying gene mutations in patients with non-M(3) acute myeloid leukemia (AML). METHODS: Second-generation sequencing was performed to detect the mutations of 22 genes in 389 patients with AML in the First Affiliated Hospital of Zhengzhou University from June 2016 to December 2018, and Kaplan-Meier and Cox regression models were used to analyze the prognostic factors. RESULTS: The mutation frequency of IDH1 and IDH2 was 6.2% and 8.7%, respectively, in all patients without co-mutation. The IDH2 mutant group had an older age, higher proportion of bone marrow primitive cells, more common normal karyotype, and more common RUNX1 and SRSF2 mutations compared with IDH2 wild-type group. Univariate analysis of variance showed that the median OS and PFS of IDH1 mutation group were significantly shorter than those of the wild-type group (P<0.05). IDH2 mutation as a single variable and IDH2R140 mutation had no significant effect on the prognosis, while different mutation sites had different effects. Compared with the IDH2 wild-type group, the IDH2R172 mutation group had lower complete remission (CR) rate and shorter median OS and PFS (P<0.05). In patients with normal karyotypes or aged ≥50 years, IDH2 mutation as a single variable had no significant effect on the prognosis, IDH1 mutation and IDH2R172 mutation were associated with poor OS and PFS (P<0.05), and IDH2R140 mutation had no significant effect on OS and PFS. Approximately 74.1% (43/58) of patients with IDH mutation simultaneously carried other gene mutations; however, the number of accompanying gene mutations had no significant effect on the prognosis. Among 58 patients with IDH mutation, the CR rate of patients with NPM1 mutation was significantly higher than that of patients in the NPM1 wild-type group (81.8% vs 36.4%, P=0.014), the median OS in patients with DNMT3A mutation was lower than that of patients with DNMT3A wild type [4.0 months (95% CI 3.8-4.2) vs 6.3 months (95% CI 2.4-10.2), P=0.041) ]. Multivariate analysis showed that age ≥60 years and white blood cell count ≥100×10(9)/L were independent risk factors for OS and PFS, while CR after two courses of treatment and hematopoietic stem cell transplantation were independent prognostic favorable factors for OS and PFS. CONCLUSION: In patients with AML (non-M(3)), IDH gene mutations often coexisted with other gene mutations, and different subtypes and accompanying gene mutations of IDH have different prognostic significance.
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spelling pubmed-79572502021-03-15 IDH不同突变亚型及伴发基因突变对急性髓系白血病患者的预后意义 Zhonghua Xue Ye Xue Za Zhi 论著 OBJECTIVE: To investigate the prognostic significance of different IDH mutations and accompanying gene mutations in patients with non-M(3) acute myeloid leukemia (AML). METHODS: Second-generation sequencing was performed to detect the mutations of 22 genes in 389 patients with AML in the First Affiliated Hospital of Zhengzhou University from June 2016 to December 2018, and Kaplan-Meier and Cox regression models were used to analyze the prognostic factors. RESULTS: The mutation frequency of IDH1 and IDH2 was 6.2% and 8.7%, respectively, in all patients without co-mutation. The IDH2 mutant group had an older age, higher proportion of bone marrow primitive cells, more common normal karyotype, and more common RUNX1 and SRSF2 mutations compared with IDH2 wild-type group. Univariate analysis of variance showed that the median OS and PFS of IDH1 mutation group were significantly shorter than those of the wild-type group (P<0.05). IDH2 mutation as a single variable and IDH2R140 mutation had no significant effect on the prognosis, while different mutation sites had different effects. Compared with the IDH2 wild-type group, the IDH2R172 mutation group had lower complete remission (CR) rate and shorter median OS and PFS (P<0.05). In patients with normal karyotypes or aged ≥50 years, IDH2 mutation as a single variable had no significant effect on the prognosis, IDH1 mutation and IDH2R172 mutation were associated with poor OS and PFS (P<0.05), and IDH2R140 mutation had no significant effect on OS and PFS. Approximately 74.1% (43/58) of patients with IDH mutation simultaneously carried other gene mutations; however, the number of accompanying gene mutations had no significant effect on the prognosis. Among 58 patients with IDH mutation, the CR rate of patients with NPM1 mutation was significantly higher than that of patients in the NPM1 wild-type group (81.8% vs 36.4%, P=0.014), the median OS in patients with DNMT3A mutation was lower than that of patients with DNMT3A wild type [4.0 months (95% CI 3.8-4.2) vs 6.3 months (95% CI 2.4-10.2), P=0.041) ]. Multivariate analysis showed that age ≥60 years and white blood cell count ≥100×10(9)/L were independent risk factors for OS and PFS, while CR after two courses of treatment and hematopoietic stem cell transplantation were independent prognostic favorable factors for OS and PFS. CONCLUSION: In patients with AML (non-M(3)), IDH gene mutations often coexisted with other gene mutations, and different subtypes and accompanying gene mutations of IDH have different prognostic significance. Editorial office of Chinese Journal of Hematology 2021-01 /pmc/articles/PMC7957250/ /pubmed/33677867 http://dx.doi.org/10.3760/cma.j.issn.0253-2727.2021.01.008 Text en 2021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
IDH不同突变亚型及伴发基因突变对急性髓系白血病患者的预后意义
title IDH不同突变亚型及伴发基因突变对急性髓系白血病患者的预后意义
title_full IDH不同突变亚型及伴发基因突变对急性髓系白血病患者的预后意义
title_fullStr IDH不同突变亚型及伴发基因突变对急性髓系白血病患者的预后意义
title_full_unstemmed IDH不同突变亚型及伴发基因突变对急性髓系白血病患者的预后意义
title_short IDH不同突变亚型及伴发基因突变对急性髓系白血病患者的预后意义
title_sort idh不同突变亚型及伴发基因突变对急性髓系白血病患者的预后意义
topic 论著
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7957250/
https://www.ncbi.nlm.nih.gov/pubmed/33677867
http://dx.doi.org/10.3760/cma.j.issn.0253-2727.2021.01.008
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