Risk Stratification of Cytogenetically Normal Acute Myeloid Leukemia With Biallelic CEBPA Mutations Based on a Multi-Gene Panel and Nomogram Model.
Risk Stratification of Cytogenetically Normal Acute Myeloid Leukemia With Biallelic CEBPA Mutations Based on a Multi-Gene Panel and Nomogram Model.
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基于多基因组和列线图模型的双等位基因 CEBPA 突变的细胞遗传学正常急性髓系白血病的风险分层
DOI：
10.3389/fonc.2021.706935
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发表时间：
2021
影响因子：
4.7
通讯作者：
Ruan GR
中科院分区：
文献类型：
--
作者：
Wu LX;Jiang H;Chang YJ;Zhou YL;Wang J;Wang ZL;Cao LM;Li JL;Sun QY;Cao SB;Lou F;Zhou T;Liu LX;Wang CC;Wang Y;Jiang Q;Xu LP;Zhang XH;Liu KY;Huang XJ;Ruan GR
大约30%的中国细胞遗传学正常的急性髓性白血病（CN-AML）患者具有双等位基因CEBPA（biCEBPA）突变。临床实践中对这些患者的预后和最佳治疗方法存在争议。在这项研究中，我们进行了236个基因的靶向区域测序在158个人与这种基因型，并构建了一个诺模图模型的基础上无白血病生存（LFS）。患者以7：3的比例随机分配至训练队列（N =111）和验证队列（N =47）。采用Kaplan-Meier法对影响预后的因素进行危险分层，探讨缓解后治疗的风险适应性。在患者中发现至少1个CEBPA以外的突变基因，突变数量与LFS（61.6% vs. 39.0%，P =0.033）、生存率（85.6% vs. 62.9%，P =0.030）和累积复发率（CIR）（38.4% vs. 59.5%，P =0.0496）相关。对白色血细胞计数、CFS 3R、KMT 2A突变和DNA甲基化相关基因进行加权，构建列线图模型，区分两个危险亚组。关于LFS，低风险患者上级优于高风险患者（培训队列中89.3% vs. 33.8%，P <0.001;验证队列中87.5% vs. 18.2%，P =0.009）。与化疗相比，异基因造血干细胞移植（allo-HSCT）5年LFS改善（89.6%比32.6%，P <0.001），生存（96.9% vs. 63.6%，P =0.001）和CIR（7.2% vs. 65.8%，P <0.001）在高危患者中，而非低危患者（LFS，77.4% vs. 88.9%，P =0.424;生存率，83.9% vs. 95.5%，P =0.173; CIR，11.7% vs. 11.1%，P =0.901）。我们的研究表明，biCEBPA mu受体阳性的CN-AML患者可以进一步分为两个危险亚组的四个因素，并建议allo-HSCT作为缓解后治疗的高危患者。这些数据将帮助医生完善biCEBPA muplatin阳性CN-AML患者的治疗决策。
Approximately 30% of Chinese individuals with cytogenetically normal acute myeloid leukemia (CN-AML) have biallelic CEBPA (biCEBPA) mutations. The prognosis and optimal therapy for these patients are controversial in clinical practice. In this study, we performed targeted region sequencing of 236 genes in 158 individuals with this genotype and constructed a nomogram model based on leukemia-free survival (LFS). Patients were randomly assigned to a training cohort (N =111) and a validation cohort (N =47) at a ratio of 7:3. Risk stratification was performed by the prognostic factors to investigate the risk-adapted post-remission therapy by Kaplan–Meier method. At least 1 mutated gene other than CEBPA was identified in patients and mutation number was associated with LFS (61.6% vs. 39.0%, P =0.033), survival (85.6% vs. 62.9%, P =0.030) and cumulative incidence of relapse (CIR) (38.4% vs. 59.5%, P =0.0496). White blood cell count, mutations in CFS3R, KMT2A and DNA methylation related genes were weighted to construct a nomogram model and differentiate two risk subgroups. Regarding LFS, low-risk patients were superior to the high-risk (89.3% vs. 33.8%, P <0.001 in training cohort; 87.5% vs. 18.2%, P =0.009 in validation cohort). Compared with chemotherapy, allogenic hematopoietic stem cell transplantation (allo-HSCT) improved 5-year LFS (89.6% vs. 32.6%, P <0.001), survival (96.9% vs. 63.6%, P =0.001) and CIR (7.2% vs. 65.8%, P <0.001) in high-risk patients but not low-risk patients (LFS, 77.4% vs. 88.9%, P =0.424; survival, 83.9% vs. 95.5%, P =0.173; CIR, 11.7% vs. 11.1%, P =0.901). Our study indicated that biCEBPA mutant-positive CN-AML patients could be further classified into two risk subgroups by four factors and allo-HSCT should be recommended for high-risk patients as post-remission therapy. These data will help physicians refine treatment decision-making in biCEBPA mutant-positive CN-AML patients.
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影响因子：
6.5
作者：
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通讯作者：
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对于首次完全缓解的中危或高危急性髓系白血病患者，半相合相关干细胞移植作为缓解后治疗优于单纯化疗
影响因子：
20.3
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Wang, Yu
影响因子：
20.3
作者：
Lavallee, Vincent-Philippe;Krosl, Jana;Sauvageau, Guy
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