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Clinical and biological implications of mutational spectrum in acute myeloid leukemia of FAB subtypes M4 and M5

Cancer Gene Therapy volume 25, pages 77–83 (2018)Cite this article

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Abstract

The mutational spectrum and molecular characteristics of acute myelomonocytic lineage leukemia, namely acute myeloid leukemia (AML) French–American–British (FAB) subtypes M4 and M5, are largely unknown. In order to explore the mutational spectrum and prognostic factors of FAB-M4 and -M5, next-generation sequencing (NGS) was performed to screen for mutated genes and fusion genes relevant to the pathogenesis of AML. Of the 63 patients enrolled in the study, 60% had more than three mutated genes. NPM1 had the highest mutation frequency, followed by DNMT3A, FLT3, NRAS, RUNX1, and TET2. Univariate analysis suggested that age ≥60 years was an independent factor for both poor event-free survival (EFS) and overall survival (OS, P = 0.009, 0.002, respectively), MYH11-CBFβ was associated with better EFS and OS (P = 0.029, 0.016, respectively). However, multivariate analysis was not able to identify any independent risk factor for survival in the cohort of FAB-M4 and -M5 patients, including peripheral white blood cell count, bone marrow blast percentage, MYH11-CBFβ, FLT3-ITD, mutations in NPM1 and DNMT3A, and allogeneic hematopoietic stem cell transplantation (allo-HSCT). Our study provided new insight into the mutational spectrum and molecular characteristics of FAB-M4 and -M5. The clinical implications of the genetic signature of FAB-M4 and -M5 need to be further elucidated by larger studies.

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Acknowledgements

This work was supported by grants from the National Natural Science Foundation of China (81500118, 61501519), the China Postdoctoral Science Foundation funded project (project No.2016M600443),  PLAGH project of Medical Big Data (Project No.2016MBD-025) and Jiangsu Province Postdoctoral Science Foundation funded project (project No.1701184B).

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Author notes

  1. These authors contributed equally: Zhiheng Cheng, Kai Hu, Lei Tian, Yifeng Dai.

  2. These authors contributed equally: Jinlong Shi, Lin Fu.

Authors and Affiliations

  1. Translational Medicine Center, Huaihe Hospital of Henan University, Kaifeng, 475000, China

    Zhiheng Cheng & Jinlong Shi

  2. Department of Hematology and Lymphoma Research Center, Peking University Third Hospital, Beijing, 100191, China

    Kai Hu, Lei Tian, Xiaoyan Ke & Lin Fu

  3. Laboratory of Environmental Medicine and Developmental Toxicology, Shantou University Medical College, Shantou, 515041, China

    Yifeng Dai

  4. Department of Medicine, William Beaumont Hospital, Royal Oak, MI, 48073, USA

    Yifan Pang

  5. Department of Clinical Laboratory, Beijing Haidian Hospital, Beijing Haidian Section of Peking University Third Hospital, Beijing, 100080, China

    Wei Cui

  6. Department of Hematology, Huaihe Hospital of Henan University, Kaifeng, 475000, China

    Hongmian Zhao, Tong Qin, Yu Han, Ning Hu, Li Chen, Chao Wang & Lin Fu

  7. Department of Respiratory, Huaihe Hospital of Henan University, Kaifeng, 475000, China

    Yijie Zhang

  8. Department of Hematology, The First Affiliated Hospital of Soochow University, Suzhou, 215006, China

    Depei Wu

  9. Department of Biomedical Engineering, Chinese PLA General Hospital, Beijing, 100853, China

    Jinlong Shi

  10. Department of Medical Big Data, Chinese PLA General Hospital, Beijing, 100853, China

    Jinlong Shi

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  1. Zhiheng Cheng
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Correspondence to Jinlong Shi or Lin Fu.

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Cheng, Z., Hu, K., Tian, L. et al. Clinical and biological implications of mutational spectrum in acute myeloid leukemia of FAB subtypes M4 and M5. Cancer Gene Ther 25, 77–83 (2018). https://doi.org/10.1038/s41417-018-0013-6

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  • DOI: https://doi.org/10.1038/s41417-018-0013-6

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