Unique morphologic and genetic characteristics of acute myeloid leukemia with chromothripsis: a clinicopathologic study from a single institution
Unique morphologic and genetic characteristics of acute myeloid leukemia with chromothripsis: a clinicopathologic study from a single institution
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DOI：
10.1016/j.humpath.2020.02.003
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发表时间：
2020-04-01
期刊：
影响因子：
3.3
通讯作者：
Sukhanova, Madina
中科院分区：
文献类型：
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作者：
Gao, Juehua;Chen, Yi-Hua;Sukhanova, Madina
染色体断裂是一种独特的基因组不稳定性类型，在各种癌症中被识别。在髓系肿瘤（MN）中，染色体断裂与不良预后和特定遗传改变（复杂核型、5 q缺失和TP 53缺失）有关。然而，临床病理特征的MN与chromothripsis尚未得到彻底的特点。我们在11例MN（9例急性髓性白血病[AML]和2例骨髓增生异常综合征[MDS]病例）中发现了染色体碎裂，并注意到所有染色体碎裂阳性AML病例均为伴有骨髓增生异常相关变化的AML（AML-MRC）。我们对伴有和不伴有染色体碎裂的AML-MRC病例进行了临床病理学和遗传学特征的比较。AML-MRC伴染色体碎裂与较低的白色血细胞和血小板计数以及较高程度的核型复杂性相关。AML-MRC中的染色体碎裂症最常涉及染色体8和11，随后扩增MYC或KMT 2A。原始细胞形态学的比较形态学评估揭示了AML-MRC伴染色体碎裂的独特特征：不同程度的细胞质空泡化、肉芽化和起泡。在AML-MRC的背景下，这些形态学标志物可能会促使更多的研究，以确定与chromothripsis的情况。(C)2020爱思唯尔公司All rights reserved.
Chromothripsis is a unique type of genomic instability and is recognized in various cancers. In myeloid neoplasms (MNs), chromothripsis was linked to poor prognosis and specific genetic alterations (complex karyotype, 5q deletions, and loss of TP53). However, the clinicopathologic features of MNs with chromothripsis have not been thoroughly characterized. We identified chromothripsis in 11 cases of MNs (9 acute myeloid leukemia [AML] and 2 myelodysplastic syndrome [MDS] cases) and noted that all chromothripsis-positive AML cases were AML with myelodysplasia-related changes (AML-MRC). We performed a comparative clinicopathologic and genetic characterization of AML-MRC cases with and without chromothripsis. AML-MRC with chromothripsis is associated with lower white blood cell and platelet counts and higher degree of karyotypic complexity. Chromothripsis in AML-MRC most frequently involves chromosomes 8 and 11 with consequent amplification of either MYC or KMT2A. Comparative morphologic assessment of blast morphology revealed unique features characteristic of AML-MRC with chromothripsis: a variable degree of cytoplasmic vacuolization, granulation, and blebbing. These morphologic markers in the context of AML-MRC may prompt additional studies to identify cases with chromothripsis. (C) 2020 Elsevier Inc. All rights reserved.