International Journal of Hematology

, Volume 91, Issue 5, pp 831–837 | Cite as

Prognostic significance of the BAALC isoform pattern and CEBPA mutations in pediatric acute myeloid leukemia with normal karyotype: a study by the Japanese Childhood AML Cooperative Study Group

  • Yasuhiro Mizushima
  • Tomohiko Taki
  • Akira Shimada
  • Yoshihiro Yui
  • Yoshimi Hiraumi
  • Hiroshi Matsubara
  • Motonobu Watanabe
  • Ken-ichiro Watanabe
  • Yuri Kamitsuji
  • Yasuhide Hayashi
  • Ichiro Tsukimoto
  • Ryoji Kobayashi
  • Keizo Horibe
  • Akio Tawa
  • Tatsutoshi Nakahata
  • Souichi AdachiEmail author
Original Article


High BAALC (brain and acute leukemia, cytoplasmic) gene expression may indicate an adverse prognosis for adults who have acute myeloid leukemia (AML) and a normal karyotype, but its prognostic significance for pediatric AML cases is unclear. Whether different BAALC isoform patterns are of prognostic significance is also unclear. Newly diagnosed AML patients with normal karyotype who were treated by the Japanese Childhood AML Cooperative Treatment Protocol AML 99 were analyzed in terms of their BAALC expression levels (n = 29), BAALC isoforms (n = 29), and CEBPA mutations (n = 49). Eleven and 18 patients exhibited high and low BAALC expression, respectively, but these groups did not differ significantly in terms of overall survival (54.6 vs. 61.1%, P = 0.55) or event-free survival (61.4 vs. 50.0%, P = 0.82). Three of these 29 patients (10.3%) expressed the exon 1-5-6-8 BAALC isoform along with the expected 1-6-8 isoform and had adverse clinical outcomes. Novel CEBPA mutations were also identified in four of 49 patients (8.2%). All four patients have maintained complete remission for at least 5 years. Thus, 1-5-6-8 isoform expression may be associated with an adverse prognosis in pediatric AML with normal karyotype. CEBPA mutations may indicate a favorable prognosis.


Pediatric AML Normal karyotype BAALC CEBPA 



The authors are grateful to all members of the Japanese Childhood AML Cooperative Study Group. We also thank to Ken Tabuchi for statistical analysis. This work was supported in part by a Grant-in-Aid for Cancer Research (16-3) from the Ministry of Health, Labor and Welfare of Japan, and in part by a Scientific Research (C) grant (17591083) from the Ministry of Education, Science, Technology, Sports, and Culture of Japan.

Supplementary material

12185_2010_585_MOESM1_ESM.tif (72 kb)
Supplementary Table 1 (TIFF 71 kb)
12185_2010_585_MOESM2_ESM.tif (54 kb)
Supplementary Fig. 1 The statistical significance was not indicated for insufficient sample numbers in AML 99 protocol between normal karyotype patients with CEBPA mutation (+) (n = 4) and mutation (-) (n = 45) with regard to their OS (100 % versus 55.4 %, P = 0.14) [A] or DFS (100 % versus 48.9 %, P = 0.09) [B] (TIFF 54 kb)


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Copyright information

© The Japanese Society of Hematology 2010

Authors and Affiliations

  • Yasuhiro Mizushima
    • 1
  • Tomohiko Taki
    • 2
  • Akira Shimada
    • 3
  • Yoshihiro Yui
    • 1
  • Yoshimi Hiraumi
    • 1
  • Hiroshi Matsubara
    • 1
  • Motonobu Watanabe
    • 1
  • Ken-ichiro Watanabe
    • 1
  • Yuri Kamitsuji
    • 4
  • Yasuhide Hayashi
    • 3
  • Ichiro Tsukimoto
    • 5
  • Ryoji Kobayashi
    • 6
  • Keizo Horibe
    • 7
  • Akio Tawa
    • 8
  • Tatsutoshi Nakahata
    • 1
  • Souichi Adachi
    • 1
    • 9
    Email author
  1. 1.Department of Pediatrics, Graduate School of MedicineKyoto UniversityKyotoJapan
  2. 2.Department of Molecular Laboratory MedicineKyoto Prefectural University of Medicine Graduate School of Medical ScienceKyotoJapan
  3. 3.Department of Hematology and OncologyGunma Children’s Medical CenterGunmaJapan
  4. 4.Department of Transfusion Medicine and Cell TherapyKyoto University HospitalKyotoJapan
  5. 5.Department of the First PediatricsToho University School of MedicineTokyoJapan
  6. 6.Department of Pediatrics, Graduate School of MedicineHokkaido UniversitySapporoJapan
  7. 7.Clinical Research CenterNational Hospital Organization Nagoya Medical CenterAichiJapan
  8. 8.Department of PediatricsNational Hospital Organization Osaka National HospitalOsakaJapan
  9. 9.Department of Human Health Sciences, Graduate School of MedicineKyoto UniversityKyotoJapan

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