CCR4 Is Rarely Expressed in CCR4-mutated T/NK-cell Lymphomas Other Than Adult T-cell Leukemia/Lymphoma
CCR4 Is Rarely Expressed in CCR4-mutated T/NK-cell Lymphomas Other Than Adult T-cell Leukemia/Lymphoma
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除成人 T 细胞白血病/淋巴瘤外，CCR4 很少在 CCR4 突变 T/NK 细胞淋巴瘤中表达
DOI：
10.1007/s12185-019-02728-5
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发表时间：
2019
期刊：
影响因子：
2.1
通讯作者：
Hiroshi Inagaki
中科院分区：
文献类型：
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作者：
Yuma Sakamoto;Keiichiro Fujii;Shunji Murase;Satsuki Nakano;Ayako Masaki;Takayuki Murase;Shigeru Kusumoto;Shinsuke Iida;Atae Utsunomiya;Ryuzo Ueda;Takashi Ishida;Hiroshi Inagaki
CCR 4在大多数成人T细胞白血病/淋巴瘤（ATL）患者的肿瘤细胞上表达。ATL患者中CCR 4基因的功能获得性突变可能与羧基末端的改变有关，这一发现导致了高效抗CCR 4抗体mogamulizumab的产生。只有少数研究报道了非ATL T/NK细胞淋巴瘤中CCR 4蛋白表达和基因组CCR 4突变。此外，CCR 4蛋白表达、基因组CCR 4突变和转录CCR 4突变之间的关联尚未得到很好的分析。方法采用免疫组化法检测226例T/NK细胞淋巴瘤中CCR 4的表达，直接测序法和SNaPshot Multiplex法检测CCR 4基因第322-348位密码子的突变。在ATL和非ATL病例中，分别有48/52（92%）和58/174（33%）例CCR 4蛋白表达阳性，分别有17/52（33%）和6/174（3.4%）例检测到基因组CCR 4突变。所有17例伴有基因组CCR 4突变的ATL病例均为CCR 4蛋白表达阳性，而6例突变的非ATL病例中有5例CCR 4蛋白表达阴性且转录CCR 4突变。这项研究表明，CCR 4表达和基因组CCR 4突变的频率以及两者之间的关联可能在ATL病例和非ATL T/NK细胞淋巴瘤之间存在显著差异。
CCR4 is expressed on tumor cells of most patients with adult T-cell leukemia/lymphoma (ATL). Gain-of-function mutations of theCCR4gene in ATL patients may be associated with alterations at the carboxyl terminus, a finding which led to a high efficacy anti-CCR4 antibody, mogamulizumab. Only a few studies have reported CCR4 protein expression and genomicCCR4mutations in non-ATL T/NK-cell lymphomas. Furthermore, an association between CCR4 protein expression, genomicCCR4mutations, and transcriptCCR4mutations has not been well analyzed. The T/NK-cell lymphomas (n= 226) enrolled in this study were examined for CCR4 expression by immunohistochemistry.CCR4mutations in the codons 322–348 were detected by direct sequencing and a SNaPshot Multiplex assay. CCR4 protein expression was positive in 48/52 (92%) and 58/174 (33%) of ATL and non-ATL cases, respectively, and genomicCCR4mutations were detected in 17/52 (33%) and 6/174 (3.4%), respectively. While all 17 ATL cases with genomicCCR4mutations were positive for CCR4 protein expression, five of six mutated non-ATL cases were negative for CCR4 protein expression and transcriptCCR4mutations. This study suggests that frequencies of CCR4 expression and genomicCCR4mutations and an association between the two may be considerably different between ATL cases and non-ATL T/NK-cell lymphomas.