Yujie Niu, Xingchun Luo, Xiaoxiao Yang, Yuancheng Guo, Xiao Tang, Long Zhao, Jinli Jian, Bei Liu
{"title":"急性髓系白血病NPM1/FLT3-ITD/DNMT3A三重突变患者的临床特点、预后及GNG4的潜在预后价值","authors":"Yujie Niu, Xingchun Luo, Xiaoxiao Yang, Yuancheng Guo, Xiao Tang, Long Zhao, Jinli Jian, Bei Liu","doi":"10.1177/10732748251359836","DOIUrl":null,"url":null,"abstract":"<p><p>IntroductionNucleophosmin 1 (<i>NPM1</i>), FMS-like tyrosine kinase 3-internal tandem duplication (<i>FLT3-ITD</i>), and de novo methyl transferase 3 A (<i>DNMT3A</i>) triple-mutated acute myeloid leukemia (AML) represents a distinct entity with poor outcomes.MethodsWe explored the gene mutation spectrum and clinical characteristics of 165 AML patients retrospectively, particularly comparing patients with <i>NPM1/FLT3-ITD/DNMT3A</i> triple-mutations and those without.ResultsOur results demonstrated significantly elevated white blood cell counts (<i>P</i> < 0.001), bone marrow blast percentages (<i>P</i> = 0.037), and platelet counts (<i>P</i> = 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 (<i>P</i> = 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<sup><i>NPM1</i>mut<i>FLT3-ITD</i>mut<i>DNMT3A</i>mut</sup> and AML<sup><i>NPM1</i>mut<i>FLT3-ITD</i>mut<i>DNMT3A</i>wt</sup>. 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 (<i>GNG4</i>) was differentially expressed between AML<sup><i>NPM1</i>mut<i>FLT3-ITD</i>mut<i>DNMT3A</i>mut</sup> and AML<sup><i>NPM1</i>mut<i>FLT3-ITD</i>mut<i>DNMT3A</i>wt</sup>, which had the most adjacent nodes among hub genes. The prognostic value of <i>GNG4</i> was further validated in AML patient samples through qRT-PCR.ConclusionClinical validation indicated a substantial downregulation of <i>GNG4</i> in AML<sup><i>NPM1</i>mut<i>FLT3-ITD</i>mut<i>DNMT3A</i>mut</sup> compared to AML<sup><i>NPM1</i>mut<i>FLT3-ITD</i>mut<i>DNMT3A</i>wt</sup> patients. Thus, <i>GNG4</i> may play a role in the low survival rate of AML<sup><i>NPM1</i>mut<i>FLT3-ITD</i>mut<i>DNMT3A</i>mut</sup> patients, offering novel insights into the prognosis, therapeutic targets, and prognostic evaluation of AML.</p>","PeriodicalId":49093,"journal":{"name":"Cancer Control","volume":"32 ","pages":"10732748251359836"},"PeriodicalIF":2.5000,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12276431/pdf/","citationCount":"0","resultStr":"{\"title\":\"Clinical Characteristics and Outcomes of Acute Myeloid Leukemia Patients Harboring <i>NPM1/FLT3-ITD/DNMT3A</i> Triple Mutations and the Potential Prognostic Value of <i>GNG4</i>.\",\"authors\":\"Yujie Niu, Xingchun Luo, Xiaoxiao Yang, Yuancheng Guo, Xiao Tang, Long Zhao, Jinli Jian, Bei Liu\",\"doi\":\"10.1177/10732748251359836\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<p><p>IntroductionNucleophosmin 1 (<i>NPM1</i>), FMS-like tyrosine kinase 3-internal tandem duplication (<i>FLT3-ITD</i>), and de novo methyl transferase 3 A (<i>DNMT3A</i>) triple-mutated acute myeloid leukemia (AML) represents a distinct entity with poor outcomes.MethodsWe explored the gene mutation spectrum and clinical characteristics of 165 AML patients retrospectively, particularly comparing patients with <i>NPM1/FLT3-ITD/DNMT3A</i> triple-mutations and those without.ResultsOur results demonstrated significantly elevated white blood cell counts (<i>P</i> < 0.001), bone marrow blast percentages (<i>P</i> = 0.037), and platelet counts (<i>P</i> = 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 (<i>P</i> = 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<sup><i>NPM1</i>mut<i>FLT3-ITD</i>mut<i>DNMT3A</i>mut</sup> and AML<sup><i>NPM1</i>mut<i>FLT3-ITD</i>mut<i>DNMT3A</i>wt</sup>. 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 (<i>GNG4</i>) was differentially expressed between AML<sup><i>NPM1</i>mut<i>FLT3-ITD</i>mut<i>DNMT3A</i>mut</sup> and AML<sup><i>NPM1</i>mut<i>FLT3-ITD</i>mut<i>DNMT3A</i>wt</sup>, which had the most adjacent nodes among hub genes. The prognostic value of <i>GNG4</i> was further validated in AML patient samples through qRT-PCR.ConclusionClinical validation indicated a substantial downregulation of <i>GNG4</i> in AML<sup><i>NPM1</i>mut<i>FLT3-ITD</i>mut<i>DNMT3A</i>mut</sup> compared to AML<sup><i>NPM1</i>mut<i>FLT3-ITD</i>mut<i>DNMT3A</i>wt</sup> patients. Thus, <i>GNG4</i> may play a role in the low survival rate of AML<sup><i>NPM1</i>mut<i>FLT3-ITD</i>mut<i>DNMT3A</i>mut</sup> patients, offering novel insights into the prognosis, therapeutic targets, and prognostic evaluation of AML.</p>\",\"PeriodicalId\":49093,\"journal\":{\"name\":\"Cancer Control\",\"volume\":\"32 \",\"pages\":\"10732748251359836\"},\"PeriodicalIF\":2.5000,\"publicationDate\":\"2025-01-01\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12276431/pdf/\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Cancer Control\",\"FirstCategoryId\":\"3\",\"ListUrlMain\":\"https://doi.org/10.1177/10732748251359836\",\"RegionNum\":4,\"RegionCategory\":\"医学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"2025/7/17 0:00:00\",\"PubModel\":\"Epub\",\"JCR\":\"Q3\",\"JCRName\":\"ONCOLOGY\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Cancer Control","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.1177/10732748251359836","RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"2025/7/17 0:00:00","PubModel":"Epub","JCR":"Q3","JCRName":"ONCOLOGY","Score":null,"Total":0}
Clinical Characteristics and Outcomes of Acute Myeloid Leukemia Patients Harboring NPM1/FLT3-ITD/DNMT3A Triple Mutations and the Potential Prognostic Value of GNG4.
IntroductionNucleophosmin 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.MethodsWe 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.ResultsOur 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 AMLNPM1mutFLT3-ITDmutDNMT3Amut and AMLNPM1mutFLT3-ITDmutDNMT3Awt. 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 AMLNPM1mutFLT3-ITDmutDNMT3Amut and AMLNPM1mutFLT3-ITDmutDNMT3Awt, which had the most adjacent nodes among hub genes. The prognostic value of GNG4 was further validated in AML patient samples through qRT-PCR.ConclusionClinical validation indicated a substantial downregulation of GNG4 in AMLNPM1mutFLT3-ITDmutDNMT3Amut compared to AMLNPM1mutFLT3-ITDmutDNMT3Awt patients. Thus, GNG4 may play a role in the low survival rate of AMLNPM1mutFLT3-ITDmutDNMT3Amut patients, offering novel insights into the prognosis, therapeutic targets, and prognostic evaluation of AML.
期刊介绍：
Cancer Control is a JCR-ranked, peer-reviewed open access journal whose mission is to advance the prevention, detection, diagnosis, treatment, and palliative care of cancer by enabling researchers, doctors, policymakers, and other healthcare professionals to freely share research along the cancer control continuum. Our vision is a world where gold-standard cancer care is the norm, not the exception.
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