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

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• 作者：Shinya Tominaga-Sato (1)
  Hideki Tsushima (2)
  Koji Ando (3)
  Hidehiro Itonaga (1)
  Yoshitaka Imaizumi (2)
  Daisuke Imanishi (2)
  Masako Iwanaga (1)
  Jun Taguchi (1)
  Takuya Fukushima (2)
  Shinichiro Yoshida (3)
  Tomoko Hata (2)
  Yukiyoshi Moriuchi (4)
  Kazutaka Kuriyama (5)
  Hiroyuki Mano (6)
  Masao Tomonaga (7)
  Yasushi Miyazaki (1)
  
• 关键词：Acute myeloid leukemia ; Normal karyotype ; Myeloperoxidase ; CEBPA mutations
• 刊名：International Journal of Hematology
• 出版年：2011
• 出版时间：July 2011
• 年：2011
• 卷：94
• 期：1
• 页码：81-89
• 全文大小：326KB
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• 作者单位：Shinya Tominaga-Sato (1)
  Hideki Tsushima (2)
  Koji Ando (3)
  Hidehiro Itonaga (1)
  Yoshitaka Imaizumi (2)
  Daisuke Imanishi (2)
  Masako Iwanaga (1)
  Jun Taguchi (1)
  Takuya Fukushima (2)
  Shinichiro Yoshida (3)
  Tomoko Hata (2)
  Yukiyoshi Moriuchi (4)
  Kazutaka Kuriyama (5)
  Hiroyuki Mano (6)
  Masao Tomonaga (7)
  Yasushi Miyazaki (1)
  
  1. Department of Hematology and Molecular Medicine Unit, Atomic Bomb Disease Institute, Nagasaki University Graduate School of Biomedical Sciences, Nagasaki, Nagasaki, Japan
  2. Department of Hematology, Nagasaki University Hospital, 1-7-1 Sakamoto, Nagasaki, 852-8501, Japan
  3. Department of Internal Medicine, Nagasaki National Medical Center, Ohmura, Nagasaki, Japan
  4. Division of Hematology, Sasebo City General Hospital, Sasebo, Nagasaki, Japan
  5. School of Health Sciences, University of the Ryukyus, Okinawa, Nishihara, Japan
  6. Division of Functional Genomics, Jichi Medical University, Shimotsuke, Tochigi, Japan
  7. Department of Hematology, Japanese Red-Cross Nagasaki Atomic Bomb Hospital, Nagasaki, Nagasaki, Japan
  

文摘

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 (?0% 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 (CEBPA double-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 CEBPA double-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.