Genetic features and efficacy of decitabine-based chemotherapy in elderly patients with acute myeloid leukemia
Genetic features and efficacy of decitabine-based chemotherapy in elderly patients with acute myeloid leukemia
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DOI：
10.1080/16078454.2021.1921434
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发表时间：
2021-01-01
期刊：
影响因子：
1.9
通讯作者：
Yu, Li
中科院分区：
文献类型：
--
作者：
Wang, Bianhong;Guan, Wei;Yu, Li
目的老年急性髓细胞白血病（AML）患者预后差，传统上认为与患者和白血病相关因素有关。然而，关于这些老年患者的遗传特征的研究还没有被整合，其不良结局的遗传机制是鲜为人知的。MethodsHere，我们使用下一代测序（NGS），以确定老年AML患者的遗传特征，并确认化疗的疗效基于分子畸变。应用NGS技术分析了111个与血液系统恶性肿瘤相关的基因突变，并比较了老年（n=52）和青年（n=161）AML患者的遗传差异。此外，结果的地西他滨为基础的化疗确定在老年patients.ResultsFrequencies的不良遗传改变，如RUNX1和二次型突变（ASXL1，STAG2和剪接体），在老年患者中要高得多，而WT 1突变的频率要低得多。此外，DNMT3A、TET2、ASXL1和IDH2等表观遗传突变在老年患者中也更常见。此外，39例老年患者接受了以地西他滨为基础的化疗，结果显示总有效率（ORR）和完全缓解率（CR）分别为76.9%和71.8%。老年AML患者中位总生存期（OS）为12个月，2年OS概率为20.5%。
ObjectivesThe outcome of elderly acute myeloid leukemia (AML) patients is poor, which was traditionally attributed to patient- and leukemia-related factors. However, studies about the genetic features of these elderly patients have not been integrated and the genetic mechanism of their poor outcome is less known.MethodsHere, we used next generation sequencing (NGS) to identify the genetic features of elderly AML patients and confirmed the efficacy of chemotherapy based on molecular aberrations. Mutations in 111 genes relevant to hematological malignancy was analysed by virtue of NGS and the genetic differences were compared between elderly (n=52) and young (n=161) AML patients. Furthermore, the outcome of decitabine-based chemotherapy was identified in elderly patients.ResultsFrequencies of adverse genetic alterations, such as RUNX1 and secondary-type mutations (ASXL1, STAG2 and spliceosome), were much higher in elderly patients, while the frequency of WT1 mutations was much lower. Moreover, epigenetic mutations such as DNMT3A, TET2, ASXL1 and IDH2, were also more common in elderly patients. Furthermore, there were 39 elderly patients receiving the decitabine-based chemotherapy, and the results showed that the overall response rate (ORR) and complete remission rate (CR) were 76.9% and 71.8%, respectively. The median overall survival (OS) for those older patients was 12 months, and the 2-year OS probability was 20.5%.DiscussionOur study provides deep understanding into the molecular mechanisms of the poor outcome of elderly AML patients.ConclusionEpigenetic mutations play an important role, and decitabine-based regimen can be used as alternative first-line chemotherapy for elderly patients.