CCR4 is rarely expressed in CCR4-mutated T/NK-cell lymphomas other than adult T-cell leukemia/lymphoma
Autor: | Yuma Sakamoto, Ayako Masaki, Atae Utsunomiya, Satsuki Nakano, Hiroshi Inagaki, Shinsuke Iida, Keiichiro Fujii, Takashi Ishida, Shunji Murase, Takayuki Murase, Ryuzo Ueda, Shigeru Kusumoto |
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Rok vydání: | 2019 |
Předmět: |
medicine.medical_specialty
Receptors CCR4 CCR4 Gene Expression Antibodies Monoclonal Humanized Lymphoma T-Cell Adult T-cell leukemia/lymphoma 03 medical and health sciences 0302 clinical medicine immune system diseases hemic and lymphatic diseases Internal medicine medicine Mogamulizumab Humans Leukemia-Lymphoma Adult T-Cell Molecular Targeted Therapy Codon Gene Hematology biology Antibodies Monoclonal medicine.disease Molecular biology Lymphoma Leukemia Gain of Function Mutation 030220 oncology & carcinogenesis biology.protein Antibody 030215 immunology medicine.drug |
Zdroj: | International Journal of Hematology. 110:389-392 |
ISSN: | 1865-3774 0925-5710 |
DOI: | 10.1007/s12185-019-02728-5 |
Popis: | CCR4 is expressed on tumor cells of most patients with adult T-cell leukemia/lymphoma (ATL). Gain-of-function mutations of the CCR4 gene 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 genomic CCR4 mutations in non-ATL T/NK-cell lymphomas. Furthermore, an association between CCR4 protein expression, genomic CCR4 mutations, and transcript CCR4 mutations has not been well analyzed. The T/NK-cell lymphomas (n = 226) enrolled in this study were examined for CCR4 expression by immunohistochemistry. CCR4 mutations 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 genomic CCR4 mutations were detected in 17/52 (33%) and 6/174 (3.4%), respectively. While all 17 ATL cases with genomic CCR4 mutations were positive for CCR4 protein expression, five of six mutated non-ATL cases were negative for CCR4 protein expression and transcript CCR4 mutations. This study suggests that frequencies of CCR4 expression and genomic CCR4 mutations and an association between the two may be considerably different between ATL cases and non-ATL T/NK-cell lymphomas. |
Databáze: | OpenAIRE |
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