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Companion gene mutations and their clinical significance in AML with double or single mutant CEBPA

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Abstract

Introduction

We report the co-mutations in AML with CEBPAsm or CEBPAdm and their clinical features in a large cohort (n = 302) of CEBPAmut AML patients.

Materials and methods

We retrospectively sequenced 112 genes in 302 patients with CEBPAmut using NGS, and studied the spectrum and clinical impact of co-mutations in CEBPAdm and CEBPAsm.

Results

① The average number of mutations in CEBPAsm and CEBPAdm AML was comparable, but not significant (P = 0.17). ② CEBPAdm patients exhibited more mutations in CSF3R (P = 0.037), GATA2 (P = 0.022), and WT1 (P = 0.046). In contrast, CEBPAsm patients more frequently harbored mutations in NPM1 (P = 0.000), FLT3-ITD (P = 0.025) and NOTCH2 (P = 0.043), as well as mutations in signaling pathways and spliceosomes (P = 0.064, P = 0.027, respectively). ③ Patients with CEBPAsm/TET2mut or CEBPAsm /GATA2mut had higher platelet counts (both P = 0.011), while patients with CEBPAdm /TET2mut had significantly higher hemoglobin levels (P = 0.009). The CR rate of patients with FLT3-ITD mutations was significantly lower in the CEBPAsm group than the CEBPAdm group (P = 0.028).

Conclusions

CEBPAsm and CEBPAdm AML are each associated with their own complex co-mutation cluster. Some co-mutations influence the clinical features and CR rate differently in patients with different CEBPA mutational status.

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Acknowledgements

The authors thank all the physicians who provided leukemia samples and clinical data.

Funding

This work was partly supported by grants from Young Scientists Foundation of Changzhou No. 2 People’s Hospital (NO.2019K002), Science and Technology Project of Changzhou Health Committee (NO.QN202035), Science and Technology Development Fund project of Nanjing Medical University (No. NMUB201), Major Science Project of Changzhou Health Commission (ZD202018), Project of science and technology support for Social development, Science and Technology Bureau of Changzhou (CE20205027), Changzhou Sci&Tech program (No.CJ20210068).

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Author notes

  1. JinYuan He and Jie Liu have contributed equally to this work.

Authors and Affiliations

  1. Department of Hematology, Affiliated Changzhou Second Hospital of Nanjing Medical University, Changzhou, 213003, China

    JinYuan He, Jie Liu, HongYing Chao, XuZhang Lu, ZhuXia Jia, MeiYu Chen & Xiaohui Cai

  2. Department of Hematology, The First Affiliated Hospital of Soochow University, Soochow, 215000, China

    HongJie Shen & Zheng Wang

  3. SuZhou Jsuniwell Medical Laboratory, Suzhou, 215000, China

    Zheng Wang

  4. Department of Hematology, Affiliated Jintan People’s Hospital of Jiangsu University, Changzhou, 213000, China

    LiuJun Cao

  5. Department of Hematology, Wuxi Second People’s Hospital, Wuxi, 214000, China

    Pin Wu

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  1. JinYuan He
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He, J., Liu, J., Shen, H. et al. Companion gene mutations and their clinical significance in AML with double or single mutant CEBPA. Int J Hematol 116, 71–80 (2022). https://doi.org/10.1007/s12185-022-03322-y

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  • DOI: https://doi.org/10.1007/s12185-022-03322-y

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