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

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Abstract

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. Methods: 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. Results: 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. Conclusion: E2F1 rs3213150 polymorphism influences the chemosensitivity and prognosis of Ara-C in Chinese AML patients.

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Data availability

The datasets generated during and/or analysed during the current study are available from the corresponding author on reasonable request.

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Funding

This work was supported by the Natural Science Foundation of Hunan Province (grant number 2021JJ41011).

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Authors and Affiliations

  1. Department of Clinical Pharmacology, Xiangya Hospital, Central South University, Changsha, 410008, China

    Yanfeng Liu, Peng Chen, Ge Chen & Xiaoping Chen

  2. Department of Hematology, Xiangya Hospital, Central South University, Changsha, 410008, China

    Yanfeng Liu

  3. National Clinical Research Center for Geriatric Disorders, Xiangya Hospital, Central South University, Changsha, 410008, China

    Yanfeng Liu & Xiaoping Chen

  4. Institute of Clinical Pharmacology, Central South University, Hunan Key Laboratory of Pharmacogenetics, Changsha, 410078, China

    Peng Chen, Ge Chen & Xiaoping Chen

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  1. Yanfeng Liu
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  2. Peng Chen
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  4. Xiaoping Chen
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Contributions

Conceptualization: CXP; Methodology: LYF, CP and CG; Writing-original draft preparation: LYF; Writing-review and editing: CXP; Funding acquisition: LYF; Supervision: CXP. All authors contributed to the article and approved the submitted version.

Corresponding author

Correspondence to Xiaoping Chen.

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Ethical approval

Approval was obtained from the ethics committee of the Institute of Clinical Pharmacology, Central South University (No. CTXY-120025–2). The procedures used in this study adhere to the tenets of the Declaration of Helsinki.

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The authors have no competing interests to declare that are relevant to the content of this article.

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Informed consent was obtained from all individual participants included in the study.

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Liu, Y., Chen, P., Chen, G. et al. E2F1 rs3213150 polymorphism influences cytarabine sensitivity and prognosis in patients with acute myeloid leukemia. Ann Hematol 102, 3345–3355 (2023). https://doi.org/10.1007/s00277-023-05431-y

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  • DOI: https://doi.org/10.1007/s00277-023-05431-y

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