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 Adachi

Research output: Contribution to journalArticle

8 Citations (Scopus)

Abstract

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.

Original languageEnglish
Pages (from-to)831-837
Number of pages7
JournalInternational Journal of Hematology
Volume91
Issue number5
DOIs
Publication statusPublished - 2010
Externally publishedYes

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Karyotype
Acute Myeloid Leukemia
Protein Isoforms
Leukemia
Pediatrics
Mutation
Brain
Clinical Protocols
Disease-Free Survival
Exons
Gene Expression
Survival

Keywords

  • BAALC
  • CEBPA
  • Normal karyotype
  • Pediatric AML

ASJC Scopus subject areas

  • Hematology
  • Medicine(all)

Cite this

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. / Mizushima, Yasuhiro; Taki, Tomohiko; Shimada, Akira; Yui, Yoshihiro; Hiraumi, Yoshimi; Matsubara, Hiroshi; Watanabe, Motonobu; Watanabe, Ken Ichiro; Kamitsuji, Yuri; Hayashi, Yasuhide; Tsukimoto, Ichiro; Kobayashi, Ryoji; Horibe, Keizo; Tawa, Akio; Nakahata, Tatsutoshi; Adachi, Souichi.

In: International Journal of Hematology, Vol. 91, No. 5, 2010, p. 831-837.

Research output: Contribution to journalArticle

Mizushima, Y, Taki, T, Shimada, A, Yui, Y, Hiraumi, Y, Matsubara, H, Watanabe, M, Watanabe, KI, Kamitsuji, Y, Hayashi, Y, Tsukimoto, I, Kobayashi, R, Horibe, K, Tawa, A, Nakahata, T & Adachi, S 2010, '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', International Journal of Hematology, vol. 91, no. 5, pp. 831-837. https://doi.org/10.1007/s12185-010-0585-x
Mizushima, Yasuhiro ; Taki, Tomohiko ; Shimada, Akira ; Yui, Yoshihiro ; Hiraumi, Yoshimi ; Matsubara, Hiroshi ; Watanabe, Motonobu ; Watanabe, Ken Ichiro ; Kamitsuji, Yuri ; Hayashi, Yasuhide ; Tsukimoto, Ichiro ; Kobayashi, Ryoji ; Horibe, Keizo ; Tawa, Akio ; Nakahata, Tatsutoshi ; Adachi, Souichi. / 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. In: International Journal of Hematology. 2010 ; Vol. 91, No. 5. pp. 831-837.
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abstract = "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.",
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AU - Mizushima, Yasuhiro

AU - Taki, Tomohiko

AU - Shimada, Akira

AU - Yui, Yoshihiro

AU - Hiraumi, Yoshimi

AU - Matsubara, Hiroshi

AU - Watanabe, Motonobu

AU - Watanabe, Ken Ichiro

AU - Kamitsuji, Yuri

AU - Hayashi, Yasuhide

AU - Tsukimoto, Ichiro

AU - Kobayashi, Ryoji

AU - Horibe, Keizo

AU - Tawa, Akio

AU - Nakahata, Tatsutoshi

AU - Adachi, Souichi

PY - 2010

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N2 - 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.

AB - 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.

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