Prognostic impact of CEBPA bZIP domain mutation in acute myeloid leukemia.
Prognostic impact of CEBPA bZIP domain mutation in acute myeloid leukemia.
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DOI：
10.1182/bloodadvances.2021004292
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发表时间：
2022-01-11
期刊：
影响因子：
7.5
通讯作者：
Yamaguchi H
中科院分区：
文献类型：
--
作者：
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
在初治AML中，即使被检测为CEBPAsm，bZIP结构域的CEBPA突变也与良好的预后相关。CCAAT/增强子结合蛋白α(CEBPAmu)突变见于10%至15%的初治急性髓系白血病(AML)病例。CEBPA双突变(CEBPAdm)与预后良好相关；然而，CEBPA单突变(CEBPAsm)似乎并不能改善预后。我们在日本AML基因测序多中心合作计划注册的1028例AML患者中研究CEBPAmu对预后的预测。研究发现，碱性亮氨酸拉链结构域(BZIP)上的CEBPAmu与预后密切相关，而bZIP结构域外的CEBPAmu与预后无关。CEBPAmu在bZIP中的存在是实现完全缓解(P<；.001)、总体生存(OS；P<；.001)和复发风险(P<；.001)较低的机会的一个强有力的指标。CEBPAmu在BZIP中的预后意义也在CEBPAsm亚组中观察到(所有患者：OS，P=.008；累积复发率，P=.063；70岁和中等风险核型的患者：OS，P=.008；累积复发率，P=.026)。对744名70岁≤患者的多因素分析表明，BZIP中CEBP-Amu是最有效的OS预测因子(危险比，0.3287；P<；.001)。CEBPAdm与bZIP中的CEBPAmu重叠，为共同致病因子。综上所述，这些发现表明bZIP中CEBPAmu是AML预后的一个强有力的标志物。它在CEBPA突变的AML的治疗分层的改进和靶向治疗方法的发展方面具有潜力。
CEBPA mutation in the bZIP domain is associated with favorable prognosis in de novo AML, even if it was detected as CEBPAsm. Mutations of CCAAT/enhancer–binding protein alpha (CEBPAmu) are found in 10% to 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 seem to improve prognosis. We investigated CEBPAmu for prognosis in 1028 patients with AML, 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 < .001), better overall survival (OS; P < .001) and a lower risk of relapse (P < .001). The prognostic significance of CEBPAmu in bZIP was also observed in the subgroup with CEBPAsm (all patients: OS, P = .008; the cumulative incidence of relapse, P = .063; patients aged ≤70 years and with intermediate-risk karyotype: OS, P = .008; cumulative incidence of relapse, P = .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 < .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.
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