TY - JOUR
T1 - NKG2D gene polymorphisms are associated with disease control of chronic myeloid leukemia by dasatinib
AU - Hara, Ryujiro
AU - Onizuka, Makoto
AU - Matsusita, Erika
AU - Kikkawa, Eri
AU - Nakamura, Yoshihiko
AU - Matsushita, Hiromichi
AU - Ohgiya, Daisuke
AU - Murayama, Hiromichi
AU - Machida, Shinichiro
AU - Ohmachi, Ken
AU - Shirasugi, Yukari
AU - Ogawa, Yoshiaki
AU - Kawada, Hiroshi
AU - Ando, Kiyoshi
N1 - Publisher Copyright:
© 2017, The Japanese Society of Hematology.
PY - 2017/11/1
Y1 - 2017/11/1
N2 - 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.
AB - 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.
KW - Chronic myeloid leukemia
KW - Natural killer cell
KW - Natural killer group 2D receptor
KW - Single nucleotide polymorphism
KW - Vav guanine nucleotide exchange factor 1
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U2 - 10.1007/s12185-017-2294-1
DO - 10.1007/s12185-017-2294-1
M3 - Article
C2 - 28795321
AN - SCOPUS:85027105661
SN - 0925-5710
VL - 106
SP - 666
EP - 674
JO - International Journal of Hematology
JF - International Journal of Hematology
IS - 5
ER -