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已发表论文
整合 NPM1 突变型急性髓系白血病中拷贝数变异谱的预后价值：一项探索性研究
Authors Zhang C, Gao L , Gong M, Liu C, Zhang D, Li Z
Received 7 August 2025
Accepted for publication 25 November 2025
Published 4 December 2025 Volume 2025:18 Pages 251—266
DOI https://doi.org/10.2147/TACG.S559124
Checked for plagiarism Yes
Review by Single anonymous peer review
Peer reviewer comments 2
Editor who approved publication: Prof. Dr. Martin Maurer
Chunxia Zhang,* Li Gao,* Ming Gong, Chundi Liu, Dongmei Zhang, Zhenling Li
Department of Hematology, China-Japan Friendship Hospital, Beijing, People’s Republic of China
*These authors contributed equally to this work
Correspondence: Zhenling Li, Department of Hematology, China-Japan Friendship Hospital, No. 2 Yinghua East Road, Beijing, People’s Republic of China, Tel +86 10 84205522, Fax +86 10 84205021, Email zryyxy2013@163.com
Background: Characteristic genetic events underpin acute myeloid leukemia (AML) heterogeneity and enable precise risk stratification. However, prognostic assessment remains ambiguous in many patients due to inadequate integration of specific genetic information.
Materials and Methods: Eighty NPM1-mutated AML patients were enrolled. Copy number alterations (CNAs) were detected via shallow whole-genome sequencing (sWGS), and concurrent mutations via targeted deep sequencing of myeloid malignancy-associated genes. Clinical and laboratory parameters were integrated with genomic data for statistical analysis, with the aim of assessing the potential clinical significance of CNA profiles in prognostic stratification.
Results: NPM1 mutation subtypes A, B, and D were the most prevalent, with all patients harboring at least two concurrent mutations (4– 5 mutations being the most frequent), and these mutations commonly co-occurred with those in FLT3, DNMT3A, TET2, IDH2, and NRAS. Forty-one samples (51%) exhibited CNAs across diverse genomic regions, with dup(18)(p11.23) identified as the most recurrent locus. No significant differences in FAB classification, hematologic parameters, demographic characteristics (gender, age), co-mutation profiles, complete remission (CR) rates, or survival outcomes were observed between the CNA-positive and CNA-negative groups. Univariate survival analysis revealed patients with ≥ 2 CNAs, or FLT3-internal tandem duplication (FLT3-ITD) had significantly shorter overall survival (OS). Notably, integrative analysis of CNAs with mutational profiles showed that patients harboring both FLT3-ITD and ≥ 2 CNAs had the poorest OS, followed by those with FLT3-ITD and < 2 CNAs, and multivariate Cox regression analysis suggests a potential association between ≥ 3 CNAs and adverse outcomes; however, given the limited sample size of cases with high CNA burden, this result should be interpreted with caution.
Conclusion: This exploratory study suggests that combining CNAs and gene mutation profiles may potentially improve the existing prognostic evaluation system for NPM1-mutated AML patients. Confirmation of these results requires additional validation in larger prospective cohorts.
Keywords: NPM1 mutation, acute myeloid leukemia, copy number alteration, prognosis
Department of Hematology, China-Japan Friendship Hospital, Beijing, People’s Republic of China
*These authors contributed equally to this work
Correspondence: Zhenling Li, Department of Hematology, China-Japan Friendship Hospital, No. 2 Yinghua East Road, Beijing, People’s Republic of China, Tel +86 10 84205522, Fax +86 10 84205021, Email zryyxy2013@163.com
Background: Characteristic genetic events underpin acute myeloid leukemia (AML) heterogeneity and enable precise risk stratification. However, prognostic assessment remains ambiguous in many patients due to inadequate integration of specific genetic information.
Materials and Methods: Eighty NPM1-mutated AML patients were enrolled. Copy number alterations (CNAs) were detected via shallow whole-genome sequencing (sWGS), and concurrent mutations via targeted deep sequencing of myeloid malignancy-associated genes. Clinical and laboratory parameters were integrated with genomic data for statistical analysis, with the aim of assessing the potential clinical significance of CNA profiles in prognostic stratification.
Results: NPM1 mutation subtypes A, B, and D were the most prevalent, with all patients harboring at least two concurrent mutations (4– 5 mutations being the most frequent), and these mutations commonly co-occurred with those in FLT3, DNMT3A, TET2, IDH2, and NRAS. Forty-one samples (51%) exhibited CNAs across diverse genomic regions, with dup(18)(p11.23) identified as the most recurrent locus. No significant differences in FAB classification, hematologic parameters, demographic characteristics (gender, age), co-mutation profiles, complete remission (CR) rates, or survival outcomes were observed between the CNA-positive and CNA-negative groups. Univariate survival analysis revealed patients with ≥ 2 CNAs, or FLT3-internal tandem duplication (FLT3-ITD) had significantly shorter overall survival (OS). Notably, integrative analysis of CNAs with mutational profiles showed that patients harboring both FLT3-ITD and ≥ 2 CNAs had the poorest OS, followed by those with FLT3-ITD and < 2 CNAs, and multivariate Cox regression analysis suggests a potential association between ≥ 3 CNAs and adverse outcomes; however, given the limited sample size of cases with high CNA burden, this result should be interpreted with caution.
Conclusion: This exploratory study suggests that combining CNAs and gene mutation profiles may potentially improve the existing prognostic evaluation system for NPM1-mutated AML patients. Confirmation of these results requires additional validation in larger prospective cohorts.
Keywords: NPM1 mutation, acute myeloid leukemia, copy number alteration, prognosis