Li Qinlu, Xing Shugang, Zhang Heng, Mao Xia, Xiao Min, Wei Jia, Wang Ying
Department of Hematology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.
Front Oncol. 2020 Nov 19;10:594732. doi: 10.3389/fonc.2020.594732. eCollection 2020.
A translocation t(14;19)(q32;q13) leading to a fusion of IGH and BCL3 which is a rare cytogenetic abnormality in CLL patients, has a more aggressive clinical course with a shorter time to first treatment (TTT) and worse overall survival (OS). To date, there is no literature reporting the identification of the t(14;19) in Chinese CLL patients and the reviewing the characteristic of all patients with this abnormality reported previously in the literature.
We first demonstrate three cases of t(14;19) translocation among the 200 CLL patients from 2017 to 2019 in our hospital. We investigated several aspects such as clinicopathologic features, cytogenetic analysis, IGHV mutations, next-generation sequencing technology (NGS), and histopathological characteristics in order to clearly define the features of this entity in Chinese patients and compare them with patients reported previously in western countries.
The clinical and pathological features of our three cases resemble those of earlier reports. All patients had atypical morphologic features and atypical immunophenotypes with low CLL scores detected by flow cytometry. All cases were unmutated in the IGHV mutations. Two cases showed complex karyotype and one case demonstrate missense mutations of TP53 and FBXW7.
In conclusion, this is the first report on IGH/BCL3-positive B-CLLs in Chinese people, which provided a comprehensive analysis of clinical and pathological characteristics. In addition to some similar clinical and laboratory features reported in the previous literature, we first found that CLL with t(14;19) has a higher possibility of being accompanied with high complex karyotype (high-CK), which is now regarded as a novel negative prognostic marker. Early identification of this abnormality in CLL patients is so important that patients can benefit from the more aggressive treatments at the onset of the disease.
14号与19号染色体易位（t(14;19)(q32;q13)）导致IGH和BCL3融合，这在慢性淋巴细胞白血病（CLL）患者中是一种罕见的细胞遗传学异常，其临床病程更具侵袭性，首次治疗时间（TTT）更短，总生存期（OS）更差。迄今为止，尚无文献报道在中国CLL患者中鉴定出t(14;19)，以及回顾先前文献中报道的所有具有这种异常的患者的特征。
我们首先展示了2017年至2019年我院200例CLL患者中的3例t(14;19)易位病例。我们调查了临床病理特征、细胞遗传学分析、IGHV突变、二代测序技术（NGS）和组织病理学特征等几个方面，以便明确中国患者中该实体的特征，并将其与西方国家先前报道的患者进行比较。
我们3例患者的临床和病理特征与早期报道相似。所有患者均具有非典型形态学特征和非典型免疫表型，通过流式细胞术检测到低CLL评分。所有病例的IGHV突变均未发生改变。2例显示复杂核型，1例显示TP53和FBXW7的错义突变。
总之，这是关于中国人IGH/BCL3阳性B-CLL的首次报道，提供了临床和病理特征的综合分析。除了先前文献报道的一些相似的临床和实验室特征外，我们首次发现t(14;19)的CLL伴有高复杂核型（high-CK）的可能性更高，现在这被视为一种新的不良预后标志物。在CLL患者中早期识别这种异常非常重要，这样患者可以在疾病发作时从更积极的治疗中获益。
