Targeted gene sequencing and transcriptome sequencing reveal characteristics of NUP98 rearrangement in pediatric acute myeloid leukemia.
NUP98 rearrangement
Acute myeloid leukemia
Clinical features
Molecular characteristics
Targeted next-generation sequencing
Journal
European journal of medical research
ISSN: 2047-783X
Titre abrégé: Eur J Med Res
Pays: England
ID NLM: 9517857
Informations de publication
Date de publication:
02 Sep 2024
02 Sep 2024
Historique:
received:
13
03
2024
accepted:
23
08
2024
medline:
3
9
2024
pubmed:
3
9
2024
entrez:
2
9
2024
Statut:
epublish
Résumé
NUP98 rearrangements (NUP98-r) are rare but overrepresented mutations in pediatric acute myeloid leukemia (AML) patients. NUP98-r is often associated with chemotherapy resistance and a particularly poor prognosis. Therefore, characterizing pediatric AML with NUP98-r to identify aberrations is critically important. Here, we retrospectively analyzed the clinicopathological features, genomic and transcriptomic landscapes, treatments, and outcomes of pediatric patients with AML. Nine patients with NUP98-r mutations were identified in our cohort of 142 patients. Ten mutated genes were detected in patients with NUP98-r. The frequency of FLT3-ITD mutations differed significantly between the groups harboring NUP98-r and those without NUP98-r (P = 0.035). Unsupervised hierarchical clustering via RNA sequencing data from 21 AML patients revealed that NUP98-r samples clustered together, strongly suggesting a distinct subtype. Compared with that in the non-NUP98-r fusion and no fusion groups, CMAHP expression was significantly upregulated in the NUP98-r samples (P < 0.001 and P = 0.001, respectively). Multivariate Cox regression analyses demonstrated that patients harboring NUP98-r (P < 0.001) and WT1 mutations (P = 0.030) had worse relapse-free survival, and patients harboring NUP98-r (P < 0.008) presented lower overall survival. These investigations contribute to the understanding of the molecular characteristics, risk stratification, and prognostic evaluation of pediatric AML patients.
Sections du résumé
BACKGROUND
BACKGROUND
NUP98 rearrangements (NUP98-r) are rare but overrepresented mutations in pediatric acute myeloid leukemia (AML) patients. NUP98-r is often associated with chemotherapy resistance and a particularly poor prognosis. Therefore, characterizing pediatric AML with NUP98-r to identify aberrations is critically important.
METHODS
METHODS
Here, we retrospectively analyzed the clinicopathological features, genomic and transcriptomic landscapes, treatments, and outcomes of pediatric patients with AML.
RESULTS
RESULTS
Nine patients with NUP98-r mutations were identified in our cohort of 142 patients. Ten mutated genes were detected in patients with NUP98-r. The frequency of FLT3-ITD mutations differed significantly between the groups harboring NUP98-r and those without NUP98-r (P = 0.035). Unsupervised hierarchical clustering via RNA sequencing data from 21 AML patients revealed that NUP98-r samples clustered together, strongly suggesting a distinct subtype. Compared with that in the non-NUP98-r fusion and no fusion groups, CMAHP expression was significantly upregulated in the NUP98-r samples (P < 0.001 and P = 0.001, respectively). Multivariate Cox regression analyses demonstrated that patients harboring NUP98-r (P < 0.001) and WT1 mutations (P = 0.030) had worse relapse-free survival, and patients harboring NUP98-r (P < 0.008) presented lower overall survival.
CONCLUSIONS
CONCLUSIONS
These investigations contribute to the understanding of the molecular characteristics, risk stratification, and prognostic evaluation of pediatric AML patients.
Identifiants
pubmed: 39223643
doi: 10.1186/s40001-024-02042-9
pii: 10.1186/s40001-024-02042-9
doi:
Substances chimiques
Nuclear Pore Complex Proteins
0
Nup98 protein, human
0
nuclear pore complex protein 98
0
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
448Subventions
Organisme : Pediatric Leukemia Diagnosis and Therapeutic Technology Research Center of Zhejiang Province
ID : JBZX-201904
Organisme : Zhejiang University Special Funds Project of Fundamental Research Funds
ID : 226-2022-00021
Organisme : Natural Science Foundation of Zhejiang Province, China
ID : LY19H190005
Informations de copyright
© 2024. The Author(s).
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