Influence of DNMT3A R882 mutations on AML prognosis determined by the allele ratio in Chinese patients
Influence of DNMT3A R882 mutations on AML prognosis determined by the allele ratio in Chinese patients
复制标题
DNMT3A R882突变对中国患者等位基因比率确定的AML预后的影响
DOI：
10.1186/s12967-019-1959-3
复制
发表时间：
2019
影响因子：
7.4
通讯作者：
Chen Xiao Ping
中科院分区：
文献类型：
--
作者：
Yuan Xiao Qing;Chen Peng;Du Yin Xiao;Zhu Ke Wei;Zhang Dao Yu;Yan Han;Liu Han;Liu Yan Ling;Cao Shan;Zhou Gan;Zeng Hui;Chen Shu Ping;Zhao Xie Lan;Yang Jing;Zeng Wen Jing;Chen Xiao Ping
背景：DNMT3A R882突变对成人急性髓性白血病（AML）预后的影响目前仍存在争议。R882等位基因比例对AML药物反应和预后的影响尚不清楚。此外，蒽环类药物是否参与R882突变引起的化学耐药尚不清楚。方法：采用焦磷酸测序法检测870例接受标准诱导治疗的成年AML患者DNMT3A R882突变。分析了突变体与诱导治疗反应和疾病预后的关系。结果：74例（8.51%）患者检测到DNMT3A R882突变，突变等位基因比例在6 ~ 50%之间。在包括阿霉素在内的第一和第二疗程诱导治疗后，与R882野生型患者相比，DNMT3A R882突变体携带者的完全缓解率显著降低（P = 0.022和P = 0.038）。与R882野生型患者相比，R882突变患者的总生存期（OS）和无病生存期（DFS）显著缩短（P = 1.92 × 10-4和P = 0.004）。R882高等位基因突变组的OS明显短于低等位基因突变组（P = 0.035）。结论：我们的研究结果表明，DNMT3A R882突变对AML预后的影响是由突变等位基因比例决定的，较高的等位基因比例预示着较差的预后，可能改善AML的风险分层。此外，DNMT3A R882突变与中国AML患者对阿克鲁比星诱导治疗的不良反应相关。
Background:The influence of DNMT3A R882 mutations on adult acute myeloid leukemia (AML) prognosis is still controversial presently. The influence of R882 allele ratio on drug response and prognosis of AML is unknown yet. Besides, it is obscure whether anthracyclines are involved in chemoresistance resulted from R882 mutations.Methods:DNMT3A R882 mutations in 870 adult AML patients receiving standard induction therapy were detected by pyrosequencing. Associations of the mutants with responses to induction therapy and disease prognosis were analyzed.Results:DNMT3A R882 mutations were detected in 74 (8.51%) patients and allele ratio of the mutations ranged from 6 to 50% in the cohort. After the first and second courses of induction therapy including aclarubicin, complete remission rates were significantly lower in carriers of the DNMT3A R882 mutants as compared with R882 wildtype patients (P = 0.022 and P = 0.038, respectively). Compared with R882 wild-type patients, those with the R882 mutations showed significantly shorter overall survival (OS) and disease-free survival (DFS) (P = 1.92 × 10-4and P = 0.004, respectively). Patients with higher allele ratio of R882 mutations showed a significantly shorter OS as compared with the lower allele ratio group (P = 0.035).Conclusion:Our results indicate that the impact of DNMT3A R882 mutations on AML prognosis was determined by the mutant-allele ratio and higher allele ratio could predict a worse prognosis, which might improve AML risk stratification. In addition, DNMT3A R882 mutations were associated with an inferior response to induction therapy with aclarubicin in Chinese AML patients.