日本語フィールド
著者：*Wakita S, Sakaguchi M, Oh I, Kako S, Toya T, Najima Y, Doki N, Kanda J, Kuroda J, Mori S, Satake A, Usuki K, Ueki T, Uoshima N, Kobayashi Y, Kawata E, Tajika K, Nagao Y, Shono K, Shibusawa M, Tadokoro J, Kayamori K, Hagihara M, Uchiyama H, Uchida N, Kubota Y, Kimura S, Nagoshi H, Ichinohe T, Kurosawa S, Motomura S, Hashimoto A, Muto H, Sato E, Ogata M, Mitsuhashi K, Ando J, Marumo A, Omori I, Fujiwara Y, Terada K, Yui S, Arai K, Kitano T, Miyata M, Kurosawa A, Mizoguchi A, Komatsu N, Fukuda T, Ohashi K, Kanda Y, Inokuchi K, Yamaguchi H題名：Prognostic impact of CEBPA bZIP domain mutation in acute myeloid leukemia 発表情報：Blood Adv 巻: 6 号: 1 ページ: 238-247キーワード：概要：Mutations of CCAAT/enhancer binding protein alpha (CEBPAmu) are found in 10-15% of de novo acute myeloid leukemia (AML) cases. Double-mutated CEBPA (CEBPAdm) is associated with a favorable prognosis; however, single-mutated CEBPA (CEBPAsm) does not appear to improve prognosis. We investigated the CEBPAmu for prognosis in 1028 AML patients, registered in the Multi-center Collaborative Program for Gene Sequencing of Japanese AML. It was found that CEBPAmu in the basic leucine zipper domain (bZIP) was strongly associated with a favorable prognosis, but CEBPAmu out of the bZIP domain was not. The presence of CEBPAmu in bZIP was a strong indicator of a higher chance of achieving complete remission (p<0.001), better overall survival (OS; p<0.001) and a lower risk of relapse (p<0.001). The prognostic significance of CEBPAmu in bZIP was also observed in the subgroup with CEBPAsm (all patients, OS: p=0.008; the cumulative incidence of relapse (CIR): p=0.063. patients aged ?70 years and with intermediate-risk karyotype, OS: p=0.008; CIR: p=0.026). Multivariate analysis of 744 patients aged ?70 years showed that CEBPAmu in bZIP was the most potent predictor of OS (hazard ratio: 0.3287; p<0.001). CEBPAdm was validated as a cofounding factor, which was overlapping with CEBPAmu in bZIP. In summary, these findings indicate that CEBPAmu in bZIP is a potent marker for AML prognosis. It holds potential in the refinement of treatment stratification and the development of targeted therapeutic approaches in CEBPA mutated AML. 抄録：英語フィールド
Author：*Wakita S, Sakaguchi M, Oh I, Kako S, Toya T, Najima Y, Doki N, Kanda J, Kuroda J, Mori S, Satake A, Usuki K, Ueki T, Uoshima N, Kobayashi Y, Kawata E, Tajika K, Nagao Y, Shono K, Shibusawa M, Tadokoro J, Kayamori K, Hagihara M, Uchiyama H, Uchida N, Kubota Y, Kimura S, Nagoshi H, Ichinohe T, Kurosawa S, Motomura S, Hashimoto A, Muto H, Sato E, Ogata M, Mitsuhashi K, Ando J, Marumo A, Omori I, Fujiwara Y, Terada K, Yui S, Arai K, Kitano T, Miyata M, Kurosawa A, Mizoguchi A, Komatsu N, Fukuda T, Ohashi K, Kanda Y, Inokuchi K, Yamaguchi HTitle：Prognostic impact of CEBPA bZIP domain mutation in acute myeloid leukemia Announcement information:Blood Adv Vol: 6 Issue: 1 Page: 238-247An abstract：Mutations of CCAAT/enhancer binding protein alpha (CEBPAmu) are found in 10-15% of de novo acute myeloid leukemia (AML) cases. Double-mutated CEBPA (CEBPAdm) is associated with a favorable prognosis; however, single-mutated CEBPA (CEBPAsm) does not appear to improve prognosis. We investigated the CEBPAmu for prognosis in 1028 AML patients, registered in the Multi-center Collaborative Program for Gene Sequencing of Japanese AML. It was found that CEBPAmu in the basic leucine zipper domain (bZIP) was strongly associated with a favorable prognosis, but CEBPAmu out of the bZIP domain was not. The presence of CEBPAmu in bZIP was a strong indicator of a higher chance of achieving complete remission (p<0.001), better overall survival (OS; p<0.001) and a lower risk of relapse (p<0.001). The prognostic significance of CEBPAmu in bZIP was also observed in the subgroup with CEBPAsm (all patients, OS: p=0.008; the cumulative incidence of relapse (CIR): p=0.063. patients aged ?70 years and with intermediate-risk karyotype, OS: p=0.008; CIR: p=0.026). Multivariate analysis of 744 patients aged ?70 years showed that CEBPAmu in bZIP was the most potent predictor of OS (hazard ratio: 0.3287; p<0.001). CEBPAdm was validated as a cofounding factor, which was overlapping with CEBPAmu in bZIP. In summary, these findings indicate that CEBPAmu in bZIP is a potent marker for AML prognosis. It holds potential in the refinement of treatment stratification and the development of targeted therapeutic approaches in CEBPA mutated AML. 