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Full-length mutation search of the TP53 gene in acute myeloid leukemia has increased significance as a prognostic factor

Annals of Hematology volume 97, pages 51–61 (2018)Cite this article

Abstract

TP53 gene abnormality has been reported to be an unfavorable prognostic factor in acute myeloid leukemia (AML). However, almost all studies of TP53 gene abnormality so far have been limited to mutation searches in the DNA binding domain. As there have been few reports examining both mutation and deletion over the full-length of the TP53 gene, the clinical characteristics of TP53 gene abnormality have not yet been clearly established. In this study, TP53 gene mutation was observed in 7.3% of the total 412 de novo AML cases (33 mutations in 30 cases), with mutation outside the DNA binding domain in eight cases (27%). TP53 gene deletion was observed in 3.1% of 358 cases. All cases had monoallelic deletion with TP53 gene mutation on the opposite allele. Multivariate analysis demonstrated that TP53 gene mutation in the DNA binding domain and outside the DNA binding domain was an independent poor prognostic factor for overall survival and relapse-free survival among the total cohort and it is also an unfavorable prognostic factor in FLT3-ITD-negative AML cases aged 70 years or below with intermediate cytogenetic prognosis. In stratified treatment, full-length search for TP53 gene mutation is therefore very important.

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  1. Kazuki Terada and Hiroki Yamaguchi contributed equally to this work

Affiliations

  1. Department of Hematology, Nippon Medical School, 1-1-5 Sendagi, Bunkyo-Ku, Tokyo, 113-8603, Japan

    Kazuki Terada, Hiroki Yamaguchi, Keiki Miyadera, Taichiro Tokura, Ikuko Omori, Atushi Marumo, Yusuke Fujiwara, Shunsuke Yui, Takeshi Ryotokuji, Yoshiki Osaki, Kunihito Arai, Tomoaki Kitano, Fumiko Kosaka, Satoshi Wakita, Hayato Tamai & Koiti Inokuchi

  2. Department of Hematology, Nagano Red Cross Hospital, Nagano, Japan

    Toshimitsu Ueki

  3. Department of Hematology, NTT Medical Center Tokyo, Tokyo, Japan

    Kensuke Usuki

  4. Department of Hematology, Japanese Red Cross Kyoto Daini Hospital, Kyoto, Japan

    Yutaka Kobayashi

  5. Department of Hematology, Yokohama Minami Kyousai Hospital, Kanagawa, Japan

    Kenji Tajika & Seiji Gomi

  6. Department of Hematopoietic Stem Cell Transplantation, National Cancer Center Hospital, Tokyo, Japan

    Saiko Kurosawa & Takahiro Fukuda

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  1. Kazuki Terada
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Correspondence to Hiroki Yamaguchi.

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The study was conducted in accordance with the Declaration of Helsinki. Informed consent was obtained from patients, and the analysis and treatments were conducted with respect for the welfare and free will of the patients. This protocol was approved by our institutional review board

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Terada, K., Yamaguchi, H., Ueki, T. et al. Full-length mutation search of the TP53 gene in acute myeloid leukemia has increased significance as a prognostic factor. Ann Hematol 97, 51–61 (2018). https://doi.org/10.1007/s00277-017-3143-2

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Keywords

  • TP53
  • Mutation
  • Acute myeloid leukemia
  • Prognostic factor
  • Whole-exome gene analysis