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Mutations of epigenetic modifier genes predict poor outcome in adult acute lymphoblastic leukemia

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Abstract

Epigenetic modifier (EM) genes play important roles in the occurrence and progression of acute lymphoblastic leukemia (ALL). However, the prognostic significance of EM mutations in ALL has not yet been thoroughly investigated. This retrospective study included 205 adult patients with ALL engaged in a pediatric-type regimen. Based on targeted next-generation sequencing, they were divided into EM mutation group (EM-mut, n = 75) and EM wild-type group (EM-wt, n = 130). The EM-mut group showed a higher positive rate of minimal residual disease (MRD) on treatment day24 and before consolidation therapy (P = 0.026, 0.020). Multivariate Cox regression analysis showed that EM-mut was an independent adverse factor for overall survival (OS) and event-free survival (EFS) (HR = 2.123, 1.742; P = 0.009, 0.007). Survival analysis revealed that the OS and EFS rates were significantly lower in the EM-mut group than in the EM-wt group (3-year OS rate, 45.8% vs. 65.0%, P = 0.0041; 3-year EFS rate, 36.7% vs. 53.2%, P = 0.011). In conclusion, EM was frequently mutated in adult ALL and was characterized by poor response to induction therapy and inferior clinical outcomes.

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The data generated during and analyzed in the study are available from the corresponding author on reasonable request.

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Acknowledgements

We thank the clinical data managers of Southern Hospital, Southern Medical University for their contribution to this project.Author contributions: OJW and ZHS contributed to the concept and design of this research. OJW, DSY and DCH brewed and collected data. CZH, CJJ, TBQ, WZW and HZC performed the statistical analyses and XXL, LJ collected and analyzed the data of other independent cohort. ZT and WZX commented critically on an advanced manuscript version regarding the interpretation of the results and the discussion. XL, and LQF offered material support and revised the paper. LQF and ZHS accessed the funding of research. OJW drafted the manuscript. All authors read and approved the final version of the manuscript. OJW and DSY are co-first authors. The data that support the findings of this study are available from the corresponding author upon request.

Funding

This study was supported by the National Natural Science Foundation of China (NSFC, 82170163, 81970147, to HSZ), the National Key Research and Development Program of China (2022YFC2502605, to LX).

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  1. Jiawang Ou and Shiyu Deng contributed equally to this work.

Authors and Affiliations

  1. Department of Hematology, Nanfang Hospital, Southern Medical University, Guangzhou, China

    Jiawang Ou, Shiyu Deng, Chenhao Ding, Zihong Cai, Junjie Chen, Zicong Huang, Xiuli Xu, Jia Li, Zhengwei Wu, Bingqing Tang, Ting Zhang, Zhixiang Wang, Ya Zhou, Li Xuan, Qifa Liu & Hongsheng Zhou

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  1. Jiawang Ou
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Contributions

OJW and ZHS contributed to the concept and design of this research. OJW, DSY and DCH brewed and collected data. CZH, CJJ, TBQ, WZW and HZC performed the statistical analyses and XXL, LJ collected and analyzed the data of other independent cohort. ZT and WZX commented critically on an advanced manuscript version regarding the interpretation of the results and the discussion. XL, and LQF offered material support and revised the paper. LQF and ZHS accessed the funding of research. OJW drafted the manuscript. All authors read and approved the final version of the manuscript. OJW and DSY are co-first authors. The data that support the findings of this study are available from the corresponding author upon request.

Corresponding author

Correspondence to Hongsheng Zhou.

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All procedures performed in this study involving human participants were in accordance with the ethical standards of the institutional and/or national research committee and with the Helsinki declaration and its later amendments or comparable ethical standards.

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This study was approved by the Ethics Committee of Southern Hospital, Southern Medical University and informed consent was obtained from all participants.

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Ou, J., Deng, S., Ding, C. et al. Mutations of epigenetic modifier genes predict poor outcome in adult acute lymphoblastic leukemia. Ann Hematol (2024). https://doi.org/10.1007/s00277-024-05681-4

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