Clinical Characteristics and Outcomes of Acute Myeloid Leukemia Patients Harboring Triple Mutations and the Potential Prognostic Value of
Introduction Nucleophosmin 1 ( NPM1 ), FMS-like tyrosine kinase 3-internal tandem duplication ( FLT3-ITD ), and de novo methyl transferase 3 A ( DNMT3A ) triple-mutated acute myeloid leukemia (AML) represents a distinct entity with poor outcomes. Methods We explored the gene mutation spectrum and cl...
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| Format: | Article |
| Language: | English |
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SAGE Publishing
2025-07-01
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| Series: | Cancer Control |
| Online Access: | https://doi.org/10.1177/10732748251359836 |
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| author | Yujie Niu MD Xingchun Luo MD Xiaoxiao Yang MD Yuancheng Guo MD Xiao Tang MD Long Zhao MD Jinli Jian MD Bei Liu MD, PhD |
| author_facet | Yujie Niu MD Xingchun Luo MD Xiaoxiao Yang MD Yuancheng Guo MD Xiao Tang MD Long Zhao MD Jinli Jian MD Bei Liu MD, PhD |
| author_sort | Yujie Niu MD |
| collection | DOAJ |
| description | Introduction Nucleophosmin 1 ( NPM1 ), FMS-like tyrosine kinase 3-internal tandem duplication ( FLT3-ITD ), and de novo methyl transferase 3 A ( DNMT3A ) triple-mutated acute myeloid leukemia (AML) represents a distinct entity with poor outcomes. Methods We explored the gene mutation spectrum and clinical characteristics of 165 AML patients retrospectively, particularly comparing patients with NPM1/FLT3-ITD/DNMT3A triple-mutations and those without. Results Our results demonstrated significantly elevated white blood cell counts ( P < 0.001), bone marrow blast percentages ( P = 0.037), and platelet counts ( P = 0.007) in the triple-mutated cohort (6.7%) compared to the non-triple-mutated patients. Furthermore, all triple-mutated cases were classified as the M4/M5 subtype of the French-American-British classification ( P = 0.017). Although no significant difference in complete remission rates was observed between the groups after initial treatment, the median overall survival for triple-mutated AML patients was only 4 months. Using the Gene Expression Omnibus (GEO) database and bioinformatics, we compared AML NPM1 mut FLT3-ITD mut DNMT3A mut and AML NPM1 mut FLT3-ITD mut DNMT3A wt . A total of 246 AML patients from the GEO dataset were included to evaluate the expression profiles of differentially expressed genes. The guanine nucleotide-binding protein subunit γ 4 ( GNG4 ) was differentially expressed between AML NPM1 mut FLT3-ITD mut DNMT3A mut and AML NPM1 mut FLT3-ITD mut DNMT3A wt , which had the most adjacent nodes among hub genes. The prognostic value of GNG4 was further validated in AML patient samples through qRT-PCR. Conclusion Clinical validation indicated a substantial downregulation of GNG4 in AML NPM1 mut FLT3-ITD mut DNMT3A mut compared to AML NPM1 mut FLT3-ITD mut DNMT3A wt patients. Thus, GNG4 may play a role in the low survival rate of AML NPM1 mut FLT3-ITD mut DNMT3A mut patients, offering novel insights into the prognosis, therapeutic targets, and prognostic evaluation of AML. |
| format | Article |
| id | doaj-art-79437a8fb2ae4eecbb666af94d2cf4b9 |
| institution | Kabale University |
| issn | 1526-2359 |
| language | English |
| publishDate | 2025-07-01 |
| publisher | SAGE Publishing |
| record_format | Article |
| series | Cancer Control |
| spelling | doaj-art-79437a8fb2ae4eecbb666af94d2cf4b92025-08-20T03:27:37ZengSAGE PublishingCancer Control1526-23592025-07-013210.1177/10732748251359836Clinical Characteristics and Outcomes of Acute Myeloid Leukemia Patients Harboring Triple Mutations and the Potential Prognostic Value of Yujie Niu MDXingchun Luo MDXiaoxiao Yang MDYuancheng Guo MDXiao Tang MDLong Zhao MDJinli Jian MDBei Liu MD, PhDIntroduction Nucleophosmin 1 ( NPM1 ), FMS-like tyrosine kinase 3-internal tandem duplication ( FLT3-ITD ), and de novo methyl transferase 3 A ( DNMT3A ) triple-mutated acute myeloid leukemia (AML) represents a distinct entity with poor outcomes. Methods We explored the gene mutation spectrum and clinical characteristics of 165 AML patients retrospectively, particularly comparing patients with NPM1/FLT3-ITD/DNMT3A triple-mutations and those without. Results Our results demonstrated significantly elevated white blood cell counts ( P < 0.001), bone marrow blast percentages ( P = 0.037), and platelet counts ( P = 0.007) in the triple-mutated cohort (6.7%) compared to the non-triple-mutated patients. Furthermore, all triple-mutated cases were classified as the M4/M5 subtype of the French-American-British classification ( P = 0.017). Although no significant difference in complete remission rates was observed between the groups after initial treatment, the median overall survival for triple-mutated AML patients was only 4 months. Using the Gene Expression Omnibus (GEO) database and bioinformatics, we compared AML NPM1 mut FLT3-ITD mut DNMT3A mut and AML NPM1 mut FLT3-ITD mut DNMT3A wt . A total of 246 AML patients from the GEO dataset were included to evaluate the expression profiles of differentially expressed genes. The guanine nucleotide-binding protein subunit γ 4 ( GNG4 ) was differentially expressed between AML NPM1 mut FLT3-ITD mut DNMT3A mut and AML NPM1 mut FLT3-ITD mut DNMT3A wt , which had the most adjacent nodes among hub genes. The prognostic value of GNG4 was further validated in AML patient samples through qRT-PCR. Conclusion Clinical validation indicated a substantial downregulation of GNG4 in AML NPM1 mut FLT3-ITD mut DNMT3A mut compared to AML NPM1 mut FLT3-ITD mut DNMT3A wt patients. Thus, GNG4 may play a role in the low survival rate of AML NPM1 mut FLT3-ITD mut DNMT3A mut patients, offering novel insights into the prognosis, therapeutic targets, and prognostic evaluation of AML.https://doi.org/10.1177/10732748251359836 |
| spellingShingle | Yujie Niu MD Xingchun Luo MD Xiaoxiao Yang MD Yuancheng Guo MD Xiao Tang MD Long Zhao MD Jinli Jian MD Bei Liu MD, PhD Clinical Characteristics and Outcomes of Acute Myeloid Leukemia Patients Harboring Triple Mutations and the Potential Prognostic Value of Cancer Control |
| title | Clinical Characteristics and Outcomes of Acute Myeloid Leukemia Patients Harboring Triple Mutations and the Potential Prognostic Value of |
| title_full | Clinical Characteristics and Outcomes of Acute Myeloid Leukemia Patients Harboring Triple Mutations and the Potential Prognostic Value of |
| title_fullStr | Clinical Characteristics and Outcomes of Acute Myeloid Leukemia Patients Harboring Triple Mutations and the Potential Prognostic Value of |
| title_full_unstemmed | Clinical Characteristics and Outcomes of Acute Myeloid Leukemia Patients Harboring Triple Mutations and the Potential Prognostic Value of |
| title_short | Clinical Characteristics and Outcomes of Acute Myeloid Leukemia Patients Harboring Triple Mutations and the Potential Prognostic Value of |
| title_sort | clinical characteristics and outcomes of acute myeloid leukemia patients harboring triple mutations and the potential prognostic value of |
| url | https://doi.org/10.1177/10732748251359836 |
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