当前位置：
X-MOL 学术
›
Blood Cancer J.
›
论文详情
Our official English website, www.x-mol.net, welcomes your
feedback! (Note: you will need to create a separate account there.)
Late relapse in acute myeloid leukemia (AML): clonal evolution or therapy-related leukemia?
Blood Cancer Journal ( IF 12.9 ) Pub Date : 2019-01-16 , DOI: 10.1038/s41408-019-0170-3 Musa Yilmaz 1 , Feng Wang 2 , Sanam Loghavi 3 , Carlos Bueso-Ramos 3 , Curtis Gumbs 2 , Latasha Little 2 , Xingzhi Song 2 , Jianhua Zhang 2 , Tapan Kadia 1 , Gautam Borthakur 1 , Elias Jabbour 1 , Naveen Pemmaraju 1 , Nicholas Short 1 , Guillermo Garcia-Manero 1 , Zeev Estrov 1 , Hagop Kantarjian 1 , Andrew Futreal 2 , Koichi Takahashi 1 , Farhad Ravandi 1
Blood Cancer Journal ( IF 12.9 ) Pub Date : 2019-01-16 , DOI: 10.1038/s41408-019-0170-3 Musa Yilmaz 1 , Feng Wang 2 , Sanam Loghavi 3 , Carlos Bueso-Ramos 3 , Curtis Gumbs 2 , Latasha Little 2 , Xingzhi Song 2 , Jianhua Zhang 2 , Tapan Kadia 1 , Gautam Borthakur 1 , Elias Jabbour 1 , Naveen Pemmaraju 1 , Nicholas Short 1 , Guillermo Garcia-Manero 1 , Zeev Estrov 1 , Hagop Kantarjian 1 , Andrew Futreal 2 , Koichi Takahashi 1 , Farhad Ravandi 1
Affiliation
|
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.
中文翻译：
急性髓细胞性白血病（AML）的晚期复发：克隆进化还是与治疗有关的白血病？
晚期复发定义为至少5年缓解后出现的复发，这种情况很少见，发生在1-3％的急性髓细胞性白血病（AML）患者中。晚期复发的潜在机制仍知之甚少。我们确定了AML患者，这些患者通过标准的诱导化学疗法达到了缓解，并且在至少五年缓解后才复发（n = 15）。在诊断（n = 10），缓解（n = 6）和首次复发（n = 10）时获得的可用骨髓样品中进行了整个外显子组测序。总共鉴定出41个驱动突变，其中11个是原发肿瘤特异性，17个复发特异性和13个共有（在原发性和复发性肿瘤样本中均检测到）。我们证明了13个共有突变中的12个在表观遗传修饰子和剪接体基因中。纵向基因组学特征显示，在10名患者中的8名患者中，始祖白血病克隆在化疗后仍然存在，并为多年后复发奠定了基础。了解白血病细胞中这种静止的机制可能有助于设计旨在增加AML患者缓解时间的未来策略。
更新日期：2019-05-16
中文翻译：
急性髓细胞性白血病（AML）的晚期复发：克隆进化还是与治疗有关的白血病？
晚期复发定义为至少5年缓解后出现的复发，这种情况很少见，发生在1-3％的急性髓细胞性白血病（AML）患者中。晚期复发的潜在机制仍知之甚少。我们确定了AML患者，这些患者通过标准的诱导化学疗法达到了缓解，并且在至少五年缓解后才复发（n = 15）。在诊断（n = 10），缓解（n = 6）和首次复发（n = 10）时获得的可用骨髓样品中进行了整个外显子组测序。总共鉴定出41个驱动突变，其中11个是原发肿瘤特异性，17个复发特异性和13个共有（在原发性和复发性肿瘤样本中均检测到）。我们证明了13个共有突变中的12个在表观遗传修饰子和剪接体基因中。纵向基因组学特征显示，在10名患者中的8名患者中，始祖白血病克隆在化疗后仍然存在，并为多年后复发奠定了基础。了解白血病细胞中这种静止的机制可能有助于设计旨在增加AML患者缓解时间的未来策略。
京公网安备 11010802027423号