Monoallelic CEBPA mutations in normal karyotype acute myeloid leukemia: independent favorable prognostic factor within NPM1 mutated patients
Monoallelic CEBPA mutations in normal karyotype acute myeloid leukemia: independent favorable prognostic factor within NPM1 mutated patients
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DOI：
10.1007/s00277-012-1423-4
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发表时间：
2012-07-01
影响因子：
3.5
通讯作者：
Spiekermann, Karsten
中科院分区：
文献类型：
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作者：
Dufour, Annika;Schneider, Friederike;Spiekermann, Karsten
我们和其他人已经证明，具有双等位基因 CEBPA 基因突变 (biCEBPA) 的细胞遗传学正常 (CN)-AML 患者代表了一个分子上独特的群体，具有良好的预后。然而，携带单等位基因 CEBPA 突变 (moCEBPA) 的患者与野生型 CEBPA 患者相比，没有表现出不同的结果，并且这些突变通常与突变的 NPM1 或 FLT3-ITD 相关。迄今为止，尚未确定分子或临床标志来区分 moCEBPA 患者与野生型 CEBPA 患者的预后。因此，我们使用 AMLCG 1999 试验中治疗的 663 名 CN-AML 患者的数据来探讨 moCEBPA 在伴随临床和分子标志物（突变的 NPM1、FLT3-ITD）背景下的预后价值。对 515 名患者进行的多重 Cox 回归调整了所有可用的潜在混杂因素，结果显示 NPM1 突变改变了 moCEBPA 在总生存期 (OS，p = 0.017) 和无事件生存期 (EFS，p = 0.011) 方面的预后价值。 MoCEBPA 对 NPM1 突变患者有益：调整后 OS 风险比 (HR) 0.09，95% 置信区间 (CI) 0.01-0.63，p = 0.016； EFS-HR (95% CI) 0.16 (0.04-0.65)，p = 0.010。相比之下，moCEBPA 对野生型 NPM1 患者没有预后影响：OS-HR (95% CI) 1.08 (0.59-1.97)，p = 0.804； EFS-HR (95% CI) 1.12 (0.64-1.96)，p = 0.682。我们没有发现 FLT3-ITD 对 moCEBPA 的预后影响有任何改变。 moCEBPA 突变的存在被证明与 NPM1 突变 CN-AML 患者的生存期延长相关。在更大规模的研究中证实这些结果将澄清额外的 moCEBPA 突变是否会影响 NPM1 突变/FLT3-ITD 阳性基因型患者的风险分层。
We and others have shown that cytogenetically normal (CN)-AML patients with biallelic CEBPA gene mutations (biCEBPA) represent a molecularly distinct group with a favorable prognosis. Patients carrying a monoallelic CEBPA mutation (moCEBPA), however, show no different outcome compared to patients with wildtype CEBPA, and these mutations are frequently associated with mutated NPM1 or FLT3-ITD. So far, no molecular or clinical hallmark has been identified to prognostically distinguish moCEBPA patients from patients with wildtype CEBPA. Therefore, we used the data of 663 CN-AML patients treated within the AMLCG 1999 trial to explore the prognostic value of moCEBPA in the context of concomitant clinical and molecular markers (mutated NPM1, FLT3-ITD). Multiple Cox regression in 515 patients adjusting for all available potential confounders revealed that the NPM1 mutation modified the prognostic value of moCEBPA with respect to overall survival (OS, p = 0.017) and event-free survival (EFS, p = 0.011). MoCEBPA was beneficial in NPM1 mutated patients: adjusted OS-hazard ratio (HR) 0.09, 95% confidence interval (CI) 0.01-0.63, p = 0.016; EFS-HR (95% CI) 0.16 (0.04-0.65), p = 0.010. In contrast, moCEBPA had no prognostic impact in patients with wildtype NPM1: OS-HR (95% CI) 1.08 (0.59-1.97), p = 0.804; EFS-HR (95% CI) 1.12 (0.64-1.96), p = 0.682. We found no prognostic effect modification for moCEBPA by FLT3-ITD. The presence of a moCEBPA mutation was shown to be associated with prolonged survival in NPM1 mutated CN-AML patients. Confirmation of these results in larger studies will clarify whether an additional moCEBPA mutation influences the risk stratification of patients with an NPM1 mutated/FLT3-ITD positive genotype.