文章：

急性髓系白血病（AML）晚期复发：克隆演化还是治疗相关性白血病？

Late relapse in acute myeloid leukemia (AML): clonal evolution or therapy-related leukemia?

原文发布日期：2019-01-16

DOI: 10.1038/s41408-019-0170-3

类型: Article

开放获取: 是

英文摘要：

Late relapse, defined as relapse arising after at least 5 years of remission, is rare and occurs in 1–3% of patients with acute myeloid leukemia (AML). The underlying mechanisms of late relapse remain poorly understood. We identified patients with AML who achieved remission with standard induction chemotherapy and relapsed after at least five years of remission (n = 15). Whole exome sequencing was performed in available bone marrow samples obtained at diagnosis (n = 10), remission (n = 6), and first relapse (n = 10). A total of 41 driver mutations were identified, of which 11 were primary tumor-specific, 17 relapse-specific, and 13 shared (detected both in primary and relapsed tumor samples). We demonstrated that 12 of 13 shared mutations were in epigenetic modifier and spliceosome genes. Longitudinal genomic characterization revealed that in eight of 10 patients the founder leukemic clone persisted after chemotherapy and established the basis of relapse years later. Understanding the mechanisms of such quiescence in leukemic cells may help designing future strategies aimed at increasing remission duration in patients with AML.

摘要翻译： 

晚期复发定义为缓解至少5年后出现的复发，在急性髓系白血病患者中较为罕见，发生率约为1%-3%。其潜在机制目前尚不明确。我们筛选出经标准诱导化疗实现缓解、且在至少五年后出现复发的AML患者（共15例），对现有诊断时（10例）、缓解期（6例）及首次复发时（10例）的骨髓样本进行全外显子测序。共鉴定出41个驱动突变，其中11个为原发肿瘤特异性突变，17个为复发特异性突变，13个为共享突变（同时在原发和复发肿瘤样本中检出）。我们证实13个共享突变中有12个位于表观遗传修饰基因和剪接体基因。纵向基因组特征分析显示，10例患者中有8例的原始白血病克隆在化疗后持续存在，并为数年后的复发奠定基础。深入理解白血病细胞这种静息状态的机制，将有助于制定延长AML患者缓解期的未来策略。

原文链接：

Late relapse in acute myeloid leukemia (AML): clonal evolution or therapy-related leukemia?