Impact of molecular heterogeneity of <italic style="font-style: italic">NPM1</italic> mutations on prognosis of acute myeloid leukemia: a clinical report of 86 cases

YU Xiaoda; GUO Jiangang; WANG An’an; LI Jiajing; LIU Bei

doi:10.16016/j.2097-0927.202507019

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Impact of molecular heterogeneity of NPM1 mutations on prognosis of acute myeloid leukemia: a clinical report of 86 cases

Clinical Medicine | 更新时间：2025-09-28

- Impact of molecular heterogeneity of NPM1 mutations on prognosis of acute myeloid leukemia: a clinical report of 86 cases
- Journal of Army Medical University Vol. 47, Issue 18, Pages: 2237-2244(2025)
- 作者机构：
  
  1.兰州大学：，第一临床医学院，甘肃兰州
  2.兰州大学：，第一医院血液科，甘肃兰州
- 作者简介：
- 基金信息：
  
  the Natural Science Foundation of Gansu Province(24JRRA297)
- DOI：10.16016/j.2097-0927.202507019
  CLC： R394.3;R730.7;R733.71
- Received：05 July 2025，
  
  Revised：2025-09-05，
  
  Accepted：08 September 2025，
  
  Published：30 September 2025
- 稿件说明：
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于晓达，郭建刚，王安安，等.核仁磷酸蛋白1突变的分子异质性对急性髓系白血病预后的影响［J］.陆军军医大学学报，2025，47（18）：2237-2244.DOI：10.16016/j.2097-0927.202507019.

YU XIAODA，GUO JIANGANG，WANG ANAN，et al.Impact of molecular heterogeneity of NPM1 mutations on prognosis of acute myeloid leukemia： a clinical report of 86 cases［J］.J Army Med Univ，2025，47（18）：2237-2244.DOI：10.16016/j.2097-0927.202507019.
于晓达，郭建刚，王安安，等.核仁磷酸蛋白1突变的分子异质性对急性髓系白血病预后的影响［J］.陆军军医大学学报，2025，47（18）：2237-2244.DOI：10.16016/j.2097-0927.202507019. DOI：

YU XIAODA，GUO JIANGANG，WANG ANAN，et al.Impact of molecular heterogeneity of NPM1 mutations on prognosis of acute myeloid leukemia： a clinical report of 86 cases［J］.J Army Med Univ，2025，47（18）：2237-2244.DOI：10.16016/j.2097-0927.202507019. DOI：

摘要

目的

探讨核仁磷酸蛋白1突变（nucleophosmin 1-mutated，

NPM1

m）的分型、变异等位基因频率（variant allele frequency， VAF）、共突变等对急性髓系白血病（acute myeloid leukemia， AML）患者预后的影响。

方法

回顾性分析2017年6月至2024年9月就诊于兰州大学第一医院血液科86例

NPM1

m-AML患者的临床资料及基因突变信息与生存情况，相关性分析采用Spearman相关系数，生存分析采用Kaplan-Meier曲线和Log-rank检验，使用Cox回归分析探究生存影响因素。

结果

NPM1

m分型为罕见分型（Rares型）的患者总生存期（overall survival，OS）较ABD型缩短（中位OS：164天

416天，

=0.043）。

NPM1

m VAF值与初诊外周血白细胞计数、乳酸脱氢酶（lactate dehydrogenase，LDH）含量呈正相关（

0.05），VAF≥0.37时OS缩短（中位OS：164天

730天，

=0.003）。合并骨髓增生异常相关基因（myelodysplasia-related gene，

）突变较

野生型预后差（中位OS：45天

395天，

0.001）、FMS样酪氨酸激酶3内部串联重复（FMS-like tyrosine kinase 3-internal tandem duplication，

FLT3-ITD

）及

DNMT3A

三突变较非三突变预后差（中位OS：173 d

483 d，

=0.007）。合并

PTPN11

突变改善预后（中位OS：395 d

240 d，

=0.027），而合并

N/KRAS

突变较野生型患者呈现出预后更好的趋势（中位OS：662 d

189 d，

=0.070），但差异无统计学意义。多因素Cox分析显示LDH（

=1.002，95%

：1.000~1.003，

=0.005）、

NPM1

m VAF值（

=2.415，95%

：1.208~4.829，

=0.013）、Rares型（

=3.037，95%

：1.134~8.136，

=0.027）、

突变（

=5.283，95%

：1.991~14.017，

0.001）为患者OS相关的独立危险因素。

结论

NPM1

m-AML的预后分层需结合

NPM1

m的分子异质性，Rares型、VAF≥0.37、合并

FLT3-ITD

及

DNMT3A

突变、

突变是不良预后因素，合并

PTPN11

突变改善患者预后，合并

N/KRAS

显示出预后更好的趋势。LDH、

NPM1

m VAF值、Rares型、

突变是影响

NPM1

m-AML患者OS的独立危险因素。

Abstract

Objective

To investigate the impact of nucleophosmin 1-mutated (

NPM1

m) subtypes

variant allele frequency (VAF) and co-mutations on the survival outcomes of patients with acute myeloid leukemia (AML).

Methods

Clinical data

mutation status

and outcomes of 86

NPM1

m-AML patients admitted in Department of Hematology

First Hospital of Lanzhou University between June 2017 and September 2024 were collected and retrospectively analyzed. Spearman correlation analysis

Kaplan-Meier curve analysis

Log-rank test

and Cox regression analysis was applied for correlation analysis

survival analysis

and factors affecting survival.

Results

The overall survival (OS) was significantly shorter in the Rares subtype of

NPM1

m than the ABD subtype (median OS: 164 d

416 d

=0.043). The VAF of

NPM1

was positively correlated with the initial peripheral blood white blood cell count and lactate dehydrogenase (LDH) level (

0.05). OS was reduced when VAF was ≥0.37 (median OS: 164 d

730 d

=0.003). The presence of myelodysplasia-related gene (

) mutations was associated with a poorer prognosis when compared to the

wild-type (median OS: 45 d

395 d

0.001). The triple mutation of FMS-like tyrosine kinase 3-internal tandem duplication (

FLT3-ITD

) and

DNMT3A

also indicated a worse prognosis than the non-triple mutation (median OS: 173 d

483 d

=0.007). The presence of

PTPN11

mutations was associated with improved OS (median OS: 395 d

240 d

=0.027)

while the patients with coexistence of N/KRAS mutations trended toward better prognosis than the wild-type patients (median OS: 662 d

189 d) though no statistical significance (

=0.070). Multivariate analysis revealed that LDH (

=1.002

95%

: 1.000~1.003

=0.005)

NPM1

m VAF (

=2.415

95%

: 1.208~4.829

=0.013)

Rares subtype (

=3.037

95%

: 1.134~8.136

=0.027)

and

mutations (

=5.283

95%

: 1.991~14.017

0.001) were independent risk factors associated with OS in the patients.

Conclusion

Molecular heterogeneity of

NPM1

m should be taken into account in prognostic stratification of

NPM1

m-AML. Factors including the Rares subtype

VAF≥0.37

coexistence of

FLT3-ITD

and

DNMT3A

mutations

and

mutations are associated with poor prognosis of

NPM1

m-AML. The presence of

PTPN11

mutations improves the prognosis

while the presence of

N/KRAS

mutations shows a trend toward better prognosis. LDH

NPM1

m VAF

Rares subtype

and

mutations are independent risk factors affecting OS of patients with

NPM1

m-AML.

关键词

Keywords

references

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⁰

Impact of molecular heterogeneity of NPM1 mutations on prognosis of acute myeloid leukemia: a clinical report of 86 cases

DOI：10.16016/j.2097-0927.202507019

摘要

Abstract

关键词

Keywords

references