Clonal dynamics in a case of acute monoblastic leukemia that later developed myeloproliferative neoplasm.
Clonal dynamics in a case of acute monoblastic leukemia that later developed myeloproliferative neoplasm.
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一例后来发展为骨髓增生性肿瘤的急性单核细胞白血病病例的克隆动力学。
DOI：
10.1007/s12185-018-2419-1
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发表时间：
2018
期刊：
影响因子：
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通讯作者：
Miyazaki Y.
中科院分区：
文献类型：
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作者：
Sato S;Itonaga H;Taguchi M;Sawayama Y;Imanishi D;Tsushima H;Hata T;Moriuchi Y;Mishima H;Kinoshita A;Yoshiura KI;Miyazaki Y.
在急性髓系白血病(AML)中，患者可能含有白血病前期造血干细胞(HSCs)，其中含有在白血病细胞中观察到的部分但不是全部突变。这些白血病前期的造血干细胞可能在诱导化疗后存活，并通过获得更多的突变而导致AML的复发。我们在此报告一位急性单核细胞白血病(AMOL)患者，他后来发展为无法分类的骨髓增生性肿瘤(MPN-U)。全外显子组测序和聚类分析表明，在临床过程中存在三个不同的主要克隆：(1)一个带有ASXL1、CBL和NPM1体细胞突变的AML克隆，可能与发病机制有关，以及GATA2、SRSF2和TET2突变；(2)一个AML缓解期克隆，只有GATA2、SRSF2和TET2突变(可能是在化疗后存活的创始克隆(白血病前HSC))；(3)一个小的亚克隆，在AMOL缓解期有JAK2突变，出现在MPN-U表现和额外的突变。这些发现表明，AML患者中的白血病前期HSC可能导致非AML髓系恶性肿瘤。这是首次分析从AMOL到MPN-U的克隆进化，这可能为研究髓系恶性肿瘤的发展提供新的视角。
In acute myeloid leukemia (AML), patients may harbor pre-leukemic hematopoietic stem cells (HSCs) containing some, but not all, of the mutations observed in the leukemic cells. These pre-leukemic HSCs may survive induction chemotherapy and contribute to AML relapse by obtaining additional mutations. We report here an acute monoblastic leukemia (AMoL) patient who later developed an unclassifiable myeloproliferative neoplasm (MPN-U). Whole-exome sequencing and cluster analysis demonstrated the presence of three distinct major clones during the clinical course: (1) an AMoL clone withASXL1,CBL, andNPM1somatic mutations, likely associated with the pathogenesis, andGATA2,SRSF2,andTET2mutations, (2) an AMoL remission clone, with mutatedGATA2,SRSF2,andTET2only (possibly the founding clone (pre-leukemic HSC) that survived chemotherapy), (3) a small subclone which hadJAK2mutation during the AMoL remission, appearing at MPN-U manifestation with additional mutations. These findings suggest that pre-leukemic HSCs in AML patients may give rise to non-AML myeloid malignancies. This is the first report to analyze the clonal evolution from AMoL to MPN-U, which may provide new insight into the development of myeloid malignancies.