Medizinische Klinik und Poliklinik I, Universitätsklinikum Carl Gustav Carus, Dresden, Germany.
Medizinische Klinik III, Klinikum Leverkusen, Leverkusen, Germany.
Blood. 2022 Jan 6;139(1):87-103. doi: 10.1182/blood.2020009680.
Biallelic mutations of the CEBPA gene (CEBPAbi) define a distinct entity associated with favorable prognosis; however, the role of monoallelic mutations (CEBPAsm) is poorly understood. We retrospectively analyzed 4708 adults with acute myeloid leukemia (AML) who had been recruited into the Study Alliance Leukemia trials, to investigate the prognostic impact of CEBPAsm. CEBPA mutations were identified in 240 patients (5.1%): 131 CEBPAbi and 109 CEBPAsm (60 affecting the N-terminal transactivation domains [CEBPAsmTAD] and 49 the C-terminal DNA-binding or basic leucine zipper region [CEBPAsmbZIP]). Interestingly, patients carrying CEBPAbi or CEBPAsmbZIP shared several clinical factors: they were significantly younger (median, 46 and 50 years, respectively) and had higher white blood cell (WBC) counts at diagnosis (median, 23.7 × 109/L and 35.7 × 109/L) than patients with CEBPAsmTAD (median age, 63 years, median WBC 13.1 × 109/L; P < .001). Co-mutations were similar in both groups: GATA2 mutations (35.1% CEBPAbi; 36.7% CEBPAsmbZIP vs 6.7% CEBPAsmTAD; P < .001) or NPM1 mutations (3.1% CEBPAbi; 8.2% CEBPAsmbZIP vs 38.3% CEBPAsmTAD; P < .001). CEBPAbi and CEBPAsmbZIP, but not CEBPAsmTAD were associated with significantly improved overall (OS; median 103 and 63 vs 13 months) and event-free survival (EFS; median, 20.7 and 17.1 months vs 5.7 months), in univariate and multivariable analyses. Additional analyses revealed that the clinical and molecular features as well as the favorable survival were confined to patients with in-frame mutations in bZIP (CEBPAbZIP-inf). When patients were classified according to CEBPAbZIP-inf and CEBPAother (including CEBPAsmTAD and non-CEBPAbZIP-inf), only patients bearing CEBPAbZIP-inf showed superior complete remission rates and the longest median OS and EFS, arguing for a previously undefined prognostic role of this type of mutation.
CEBPA 基因的双等位基因突变（CEBPAbi）定义了一种与预后良好相关的独特实体；然而，单等位基因突变（CEBPAsm）的作用尚未完全了解。我们回顾性分析了 4708 名急性髓系白血病（AML）成人患者，这些患者被招募到研究联盟白血病试验中，以研究 CEBPAsm 的预后影响。在 240 名患者（5.1%）中发现了 CEBPA 突变：131 名 CEBPAbi 和 109 名 CEBPAsm（60 名影响 N 端转录激活结构域[CEBPAsmTAD]，49 名影响 C 端 DNA 结合或碱性亮氨酸拉链区[CEBPAsmbZIP]）。有趣的是，携带 CEBPAbi 或 CEBPAsmbZIP 的患者具有一些共同的临床特征：他们明显更年轻（中位年龄分别为 46 岁和 50 岁），诊断时白细胞（WBC）计数更高（中位数分别为 23.7×109/L 和 35.7×109/L），而携带 CEBPAsmTAD 的患者中位年龄为 63 岁，中位 WBC 为 13.1×109/L；P<.001）。两组的共突变相似：GATA2 突变（35.1%CEBPAbi；36.7%CEBPAsmbZIP 与 6.7%CEBPAsmTAD；P<.001）或 NPM1 突变（3.1%CEBPAbi；8.2%CEBPAsmbZIP 与 38.3%CEBPAsmTAD；P<.001）。CEBPAbi 和 CEBPAsmbZIP，但不是 CEBPAsmTAD，与总生存（OS；中位 103 个月和 63 个月）和无事件生存（EFS；中位 20.7 个月和 17.1 个月）明显相关，这在单变量和多变量分析中都得到了证实。进一步的分析表明，临床和分子特征以及有利的生存仅限于 bZIP 中有框突变（CEBPAbZIP-inf）的患者。当根据 CEBPAbZIP-inf 和 CEBPAother（包括 CEBPAsmTAD 和非 CEBPAbZIP-inf）对患者进行分类时，只有携带 CEBPAbZIP-inf 的患者表现出更高的完全缓解率和最长的中位 OS 和 EFS，这表明这种类型的突变具有以前未定义的预后作用。
