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
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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.
KeywordsPediatric 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.
- 2.Shimada A, Taki T, Tabuchi K, Taketani T, Hanada R, Tawa A, et al. Tandem duplications of MLL and FLT3 are correlated with poor prognosis in pediatric acute myeloid leukemia: a study of the Japanese childhood AML Cooperative Study Group. Pediatr Blood Cancer. 2008;50:264–9.CrossRefPubMedGoogle Scholar
- 9.Mrózek K, Marcucci G, Paschka P, Whitman SP, Bloomfield CD. Clinical relevance of mutations and gene-expression changes in adult acute myeloid leukemia with normal cytogenetics: are we ready for a prognostically prioritized molecular classification? Blood. 2007;109:431–48.CrossRefPubMedGoogle Scholar
- 17.Barjesteh van Waalwijk van Doorn-Khosrovani S, Erpelinck C, van Putten WL, Valk PJ, van der Poel-van de Luytgaarde S, Hack R, et al. High EVI1 expression predicts poor survival in acute myeloid leukemia: a study of 319 de novo AML patients. Blood. 2003;101:837–45.Google Scholar
- 26.Shimada A, Taki T, Tabuchi K, Tawa A, Horibe K, Tsuchida M, et al. KIT mutations, and not FLT3 internal tandem duplication, are strongly associated with a poor prognosis in pediatric acute myeloid leukemia with t(8;21): a study of the Japanese Childhood AML Cooperative Study Group. Blood. 2006;107:1806–9.CrossRefPubMedGoogle Scholar
- 27.Tsukimoto I, Tawa A, Horibe K, Tabuchi K, Kigasawa H, Tsuchida M, et al. Risk-stratified therapy and the intensive use of cytarabine improves the outcome in childhood acute myeloid leukemia: the AML99 trial from the Japanese Childhood AML Cooperative Study Group. J Clin Oncol. 2009;27:4007–13.CrossRefPubMedGoogle Scholar
- 29.Najima Y, Ohashi K, Kawamura M, Onozuka Y, Yamaguchi T, Akiyama H, et al. Molecular monitoring of BAALC expression in patients with CD34-positive acute leukemia. Int J Hematol. 2010. doi: 10.1007/s12185-010-0550-8.
- 32.Wang X, Tian QB, Okano A, Sakagami H, Moon IS, Kondo H, et al. BAALC 1-6-8 protein is targeted to postsynaptic lipid rafts by its N-terminal myristoylation and palmitoylation, and interacts with alpha, but not beta, subunit of Ca/calmodulin-dependent protein kinase II. J Neurochem. 2005;92:647–59.CrossRefPubMedGoogle Scholar
- 37.Wouters BJ, Löwenberg B, Erpelinck-Verschueren CA, van Putten WL, Valk PJ, Delwel R. Double CEBPA mutations, but not single CEBPA mutations, define a subgroup of acute myeloid leukemia with a distinctive gene expression profile that is uniquely associated with a favorable outcome. Blood. 2009;113:3088–91.CrossRefPubMedGoogle Scholar