E2F1 rs3213150 polymorphism influences cytarabine sensitivity and prognosis in patients with acute myeloid leukemia.


Journal

Annals of hematology
ISSN: 1432-0584
Titre abrégé: Ann Hematol
Pays: Germany
ID NLM: 9107334

Informations de publication

Date de publication:
Dec 2023
Historique:
received: 06 06 2023
accepted: 26 08 2023
medline: 13 11 2023
pubmed: 4 9 2023
entrez: 4 9 2023
Statut: ppublish

Résumé

Cytarabine (Ara-C) plays an irreplaceable role in the treatment of acute myeloid leukemia (AML). However, there are significant differences in efficacy among patients. Our previous studies found that E2F1 rs3213150 polymorphism was associated with remission rate of Ara-C chemotherapy, but the specific mechanism is not clear. This study aimed to further confirm the correlation between E2F1 rs3213150 polymorphism and Ara-C resistance and prognosis in AML patients, and to provide valuable information for elucidating the molecular mechanisms involved. Rs3213150 genotyping was performed in 922 AML patients by Sanger sequencing, and the effects of different genotypes on chemosensitivity and prognosis were analyzed by Logistic regression and Cox regression. Meanwhile, a prediction model of Ara-C chemotherapy resistance was established. The impact of rs3213150 polymorphism on E2F1 expression level was determined by luciferase reporter gene assay, and differentially expressed genes between patients with different genotypes were identified by RNA sequencing. Compared with rs3213150 G allele carriers, patients with AA genotype had more obvious Ara-C resistance (41.94% vs. 27.94%, P = 0.002), shorter overall survival (529 d vs. 644 d, P = 0.008) and disease-free survival (519 d vs. 556 d, P = 0.023). Rs3213150G > A mutation resulted in decreased E2F1 expression. E2F1 rs3213150 polymorphism influences the chemosensitivity and prognosis of Ara-C in Chinese AML patients.

Identifiants

pubmed: 37665348
doi: 10.1007/s00277-023-05431-y
pii: 10.1007/s00277-023-05431-y
doi:

Substances chimiques

Cytarabine 04079A1RDZ
E2F1 protein, human 0
E2F1 Transcription Factor 0

Types de publication

Journal Article

Langues

eng

Sous-ensembles de citation

IM

Pagination

3345-3355

Subventions

Organisme : Natural Science Foundation of Hunan Province
ID : 2021JJ41011

Informations de copyright

© 2023. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.

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Auteurs

Yanfeng Liu (Y)

Department of Clinical Pharmacology, Xiangya Hospital, Central South University, Changsha, 410008, China.
Department of Hematology, Xiangya Hospital, Central South University, Changsha, 410008, China.
National Clinical Research Center for Geriatric Disorders, Xiangya Hospital, Central South University, Changsha, 410008, China.

Peng Chen (P)

Department of Clinical Pharmacology, Xiangya Hospital, Central South University, Changsha, 410008, China.
Institute of Clinical Pharmacology, Central South University, Hunan Key Laboratory of Pharmacogenetics, Changsha, 410078, China.

Ge Chen (G)

Department of Clinical Pharmacology, Xiangya Hospital, Central South University, Changsha, 410008, China.
Institute of Clinical Pharmacology, Central South University, Hunan Key Laboratory of Pharmacogenetics, Changsha, 410078, China.

Xiaoping Chen (X)

Department of Clinical Pharmacology, Xiangya Hospital, Central South University, Changsha, 410008, China. chenxiaoping@csu.edu.cn.
National Clinical Research Center for Geriatric Disorders, Xiangya Hospital, Central South University, Changsha, 410008, China. chenxiaoping@csu.edu.cn.
Institute of Clinical Pharmacology, Central South University, Hunan Key Laboratory of Pharmacogenetics, Changsha, 410078, China. chenxiaoping@csu.edu.cn.

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