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09.08.2017 | Original Article

NKG2D gene polymorphisms are associated with disease control of chronic myeloid leukemia by dasatinib

verfasst von: Ryujiro Hara, Makoto Onizuka, Erika Matsusita, Eri Kikkawa, Yoshihiko Nakamura, Hiromichi Matsushita, Daisuke Ohgiya, Hiromichi Murayama, Shinichiro Machida, Ken Ohmachi, Yukari Shirasugi, Yoshiaki Ogawa, Hiroshi Kawada, Kiyoshi Ando

Erschienen in: International Journal of Hematology | Ausgabe 5/2017

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Abstract

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.

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Titel: NKG2D gene polymorphisms are associated with disease control of chronic myeloid leukemia by dasatinib
verfasst von: Ryujiro Hara
Makoto Onizuka
Erika Matsusita
Eri Kikkawa
Yoshihiko Nakamura
Hiromichi Matsushita
Daisuke Ohgiya
Hiromichi Murayama
Shinichiro Machida
Ken Ohmachi
Yukari Shirasugi
Yoshiaki Ogawa
Hiroshi Kawada
Kiyoshi Ando
Publikationsdatum: 09.08.2017
Verlag: Springer Japan
Erschienen in: International Journal of Hematology / Ausgabe 5/2017
Print ISSN: 0925-5710
Elektronische ISSN: 1865-3774
DOI: https://doi.org/10.1007/s12185-017-2294-1

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NKG2D gene polymorphisms are associated with disease control of chronic myeloid leukemia by dasatinib

Abstract

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