TY - JOUR
T1 - Prognostic significance of the BAALC isoform pattern and CEBPA mutations in pediatric acute myeloid leukemia with normal karyotype
T2 - A study by the Japanese Childhood AML Cooperative Study Group
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
N1 - Funding Information:
Acknowledgments 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.
PY - 2010/6
Y1 - 2010/6
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.
KW - BAALC
KW - CEBPA
KW - Normal karyotype
KW - Pediatric AML
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U2 - 10.1007/s12185-010-0585-x
DO - 10.1007/s12185-010-0585-x
M3 - Article
C2 - 20495894
AN - SCOPUS:77954497925
VL - 91
SP - 831
EP - 837
JO - International Journal of Hematology
JF - International Journal of Hematology
SN - 0925-5710
IS - 5
ER -