NKG2D gene polymorphisms are associated with disease control of chronic myeloid leukemia by dasatinib
| Autor: | Daisuke Ohgiya, Yukari Shirasugi, Erika Matsusita, Eri Kikkawa, Yoshiaki Ogawa, Ken Ohmachi, Shinichiro Machida, Kiyoshi Ando, Hiroshi Kawada, Ryujiro Hara, Makoto Onizuka, Hiromichi Matsushita, Hiromichi Murayama, Yoshihiko Nakamura |
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| Rok vydání: | 2017 |
| Předmět: |
0301 basic medicine
Male medicine.medical_specialty VAV1 Lymphocytosis Dasatinib chemical and pharmacologic phenomena Single-nucleotide polymorphism Biology Natural killer cell 03 medical and health sciences 0302 clinical medicine Internal medicine Leukemia Myelogenous Chronic BCR-ABL Positive medicine Biomarkers Tumor Humans Alleles Hematology Polymorphism Genetic Myeloid leukemia Middle Aged NKG2D Neoplasm Proteins 030104 developmental biology medicine.anatomical_structure NK Cell Lectin-Like Receptor Subfamily K 030220 oncology & carcinogenesis Immunology Cancer research Female medicine.symptom medicine.drug |
| Zdroj: | International journal of hematology. 106(5) |
| ISSN: | 1865-3774 |
| Popis: | A recent study reported that treatment-free remission (TFR) of chronic myeloid leukemia (CML) after dasatinib (Das) treatment was significantly associated with natural killer (NK) cell proliferation in the peripheral blood. However, biomarkers to predict lymphocytosis or successful TFR are not well characterized. In order to clarify individual differences in NK cell responses among patients treated with Das, we retrospectively analyzed the association between polymorphisms in the natural killer group 2D receptor [NKG2D; also known as killer cell lectin like receptor K1 (KLRK1)] gene and clinical outcomes in 31 patients treated with Das as first-line treatment for CML. Patients with the NKG2D HNK1/HNK1 (high-cytotoxic activity-related allele on NKG2D hb-1) haplotype achieved MR4.5 more quickly than those with other haplotypes [hazard ratio (HR) 4.39; 95% confidence interval (CI) 2.75–118.6; P = 0.004]. In addition, NK cells with the NKG2D HNK1 allele exhibited enhanced phosphorylation of vav guanine nucleotide exchange factor 1 (VAV1) at Tyr174. These data suggest that NKG2D gene polymorphisms may represent candidate biomarkers for the prediction of TFR following Das treatment. |
| Databáze: | OpenAIRE |
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