International Journal of Hematology

, Volume 94, Issue 1, pp 81–89

Expression of myeloperoxidase and gene mutations in AML patients with normal karyotype: double CEBPA mutations are associated with high percentage of MPO positivity in leukemic blasts

Authors

  • Shinya Tominaga-Sato
    • Department of Hematology and Molecular Medicine Unit, Atomic Bomb Disease InstituteNagasaki University Graduate School of Biomedical Sciences
    • Department of HematologyNagasaki University Hospital
  • Koji Ando
    • Department of Internal MedicineNagasaki National Medical Center
  • Hidehiro Itonaga
    • Department of Hematology and Molecular Medicine Unit, Atomic Bomb Disease InstituteNagasaki University Graduate School of Biomedical Sciences
  • Yoshitaka Imaizumi
    • Department of HematologyNagasaki University Hospital
  • Daisuke Imanishi
    • Department of HematologyNagasaki University Hospital
  • Masako Iwanaga
    • Department of Hematology and Molecular Medicine Unit, Atomic Bomb Disease InstituteNagasaki University Graduate School of Biomedical Sciences
  • Jun Taguchi
    • Department of Hematology and Molecular Medicine Unit, Atomic Bomb Disease InstituteNagasaki University Graduate School of Biomedical Sciences
  • Takuya Fukushima
    • Department of HematologyNagasaki University Hospital
  • Shinichiro Yoshida
    • Department of Internal MedicineNagasaki National Medical Center
  • Tomoko Hata
    • Department of HematologyNagasaki University Hospital
  • Yukiyoshi Moriuchi
    • Division of HematologySasebo City General Hospital
  • Kazutaka Kuriyama
    • School of Health SciencesUniversity of the Ryukyus
  • Hiroyuki Mano
    • Division of Functional GenomicsJichi Medical University
  • Masao Tomonaga
    • Department of HematologyJapanese Red-Cross Nagasaki Atomic Bomb Hospital
  • Yasushi Miyazaki
    • Department of Hematology and Molecular Medicine Unit, Atomic Bomb Disease InstituteNagasaki University Graduate School of Biomedical Sciences
Original Article

DOI: 10.1007/s12185-011-0883-y

Cite this article as:
Tominaga-Sato, S., Tsushima, H., Ando, K. et al. Int J Hematol (2011) 94: 81. doi:10.1007/s12185-011-0883-y

Abstract

The percentage of myeloperoxidase (MPO)-positive blast cells is a simple and highly significant prognostic factor in AML patients. It has been reported that the high MPO group (MPO-H), in which >50% of blasts are MPO activity positive, is associated with favorable karyotypes, while the low MPO group (≤50% of blasts are MPO activity positive, MPO-L) is associated with adverse karyotypes. The MPO-H group shows better survival even when restricted to patients belonging to the intermediate chromosomal risk group or those with a normal karyotype. It has recently been shown that genotypes defined by the mutational status of NPM1, FLT3, and CEBPA are associated with treatment outcome in patients with cytogenetically normal AML. In this study, we aimed to evaluate the relationship between MPO positivity and gene mutations found in normal karyotypes. Sixty AML patients with normal karyotypes were included in this study. Blast cell MPO positivity was assessed in bone marrow smears stained for MPO. Associated genetic lesions (the NPM1, FLT3-ITD, and CEBPA mutations) were studied using nucleotide sequencing. Thirty-two patients were in the MPO-L group, and 28 patients in the MPO-H group. FLT3-ITD was found in 11 patients (18.3%), NPM1 mutations were found in 19 patients (31.7%), and CEBPA mutations were found in 11 patients (18.3%). In patients with CEBPA mutations, the carrying two simultaneous mutations (CEBPAdouble-mut) was associated with high MPO expression, while the mutant NPM1 without FLT3-ITD genotype was not associated with MPO activity. Both higher MPO expression and the CEBPAdouble-mut genotype appeared to be associated with improved overall survival after intensive chemotherapy. Further studies are required to determine the importance of blast MPO activity as a prognostic factor, especially in CEBPA wild-type patients with a normal karyotype.

Keywords

Acute myeloid leukemiaNormal karyotypeMyeloperoxidaseCEBPA mutations

Copyright information

© The Japanese Society of Hematology 2011