Clinicopathologic Characterization of Aggressive Natural Killer Cell Leukemia Involving Different Tissue Sites
Clinicopathologic Characterization of Aggressive Natural Killer Cell Leukemia Involving Different Tissue Sites
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DOI：
10.1097/pas.0000000000000634
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发表时间：
2016-06-01
影响因子：
5.6
通讯作者：
Wang, Jian Chao
中科院分区：
文献类型：
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作者：
Gao, Li-Min;Zhao, Sha;Wang, Jian Chao
侵袭性自然杀伤细胞白血病（ANKL）是一种罕见的疾病，具有非常积极的临床过程。ANKL的病因尚不清楚，迄今为止描述的遗传/表观遗传畸变很少。此外，ANKL的误诊是一个常见的问题。回顾性分析35例ANKL患者的临床病理特征，旨在提高诊断水平，并寻找与ANKL病因相关的遗传/表观遗传畸变。由于外周血和骨髓中的白血病细胞数量相对较低，ANKL的诊断可能会被遗漏;因此，必要时对实体组织进行活检是很重要的。我们描述了ANKL在淋巴结、骨髓、脾、肝和皮肤中的病理学，重点是诊断和鉴别诊断。我们观察到年轻男性在我们的队列中占优势，临床过程比以前报道的更具侵略性。低乳酸脱氢酶（< 712 IU/L）、化疗或L-天冬酰胺酶给药与更有利的结局相关。还筛选了STAT 5 B和STAT 3的SH 2结构域是否存在活化突变。此外，在ANKL样品中测定了候选肿瘤抑制基因HACE 1的CpG岛甲基化状态。我们在ANKL病例中观察到激活性STAT 5 B突变（1/5）和HACE 1高甲基化（3/4），表明这些畸变可能有助于ANKL发病机制。
Aggressive natural killer cell leukemia (ANKL) is a rare disease with an extremely aggressive clinical course. The etiology of ANKL is unclear with few genetic/epigenetic aberrations described to date. Moreover, misdiagnosis of ANKL is a frequent problem. Clinicopathologic characteristics of 35 retrospective cases of ANKL were investigated with the aim of improving diagnosis and to find the genetic/epigenetic aberrations associated with ANKL etiology. Because of the relatively low number of leukemic cells in the peripheral blood and bone marrow, diagnosis of ANKL can be missed; therefore, it is important to perform biopsy on solid tissues, if necessary. We describe the pathology of ANKL in the lymph nodes, bone marrow, spleen, liver, and skin, with focus on diagnosis and differentiated diagnosis. We observed young male predominance in our cohort, and the clinical course was more aggressive than reported previously. Low lactate dehydrogenase (< 712 IU/L), chemotherapy or L-asparaginase administration were found to be associated with more favorable outcomes. SH2 domains of STAT5B and STAT3 also were screened for the presence of activating mutations. Moreover, CpG island methylation status of HACE1, a candidate tumor-suppressor gene, was determined in ANKL samples. We observed activating STAT5B mutations (1/5) and hypermethylation of HACE1 (3/4) in ANKL cases, suggesting that these aberrations may contribute to ANKL pathogenesis.