International Journal of Hematology

, Volume 106, Issue 5, pp 666–674 | Cite as

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

  • Ryujiro Hara
  • Makoto OnizukaEmail author
  • Erika Matsusita
  • Eri Kikkawa
  • Yoshihiko Nakamura
  • Hiromichi Matsushita
  • Daisuke Ohgiya
  • Hiromichi Murayama
  • Shinichiro Machida
  • Ken Ohmachi
  • Yukari Shirasugi
  • Yoshiaki Ogawa
  • Hiroshi Kawada
  • Kiyoshi Ando
Original Article


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.


Chronic myeloid leukemia Natural killer cell Natural killer group 2D receptor Vav guanine nucleotide exchange factor 1 Single nucleotide polymorphism 



The results of this study were presented in part at the 78th Japanese Society of Hematology Annual Meeting in Yokohama, Kanagawa, Japan, October 13–15, 2016 (Abstract Number OS-2-89), and at the 58th ASH Annual Meeting and Exposition in San Diego, CA, December 3–6, 2016 (Abstract Number 3091). The authors thank Inter-Biotech for help with the English language editing of this paper.

Author contributions

MO, EM, YN, HM, and KA designed the research study. MO, DO, HM, SM, KO, YS, YO, HK, and KA provided patients for the study. RH, MO, EM, EK, and YN were involved in the collection and analysis of the data. RH, MO, YN, and KA wrote the paper. All authors were involved in revising the manuscript and approved the final version.

Compliance with ethical standards

Funding source

This research did not receive any specific grant from funding agencies in the public, commercial, or not-for-profit sectors.

Conflict of interest

The authors declare that they have no conflict of interest. A summary of relevant information will be published with the manuscript.


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Copyright information

© The Japanese Society of Hematology 2017

Authors and Affiliations

  • Ryujiro Hara
    • 1
  • Makoto Onizuka
    • 1
    • 2
    Email author
  • Erika Matsusita
    • 1
  • Eri Kikkawa
    • 1
  • Yoshihiko Nakamura
    • 2
  • Hiromichi Matsushita
    • 3
  • Daisuke Ohgiya
    • 1
  • Hiromichi Murayama
    • 1
  • Shinichiro Machida
    • 1
  • Ken Ohmachi
    • 1
  • Yukari Shirasugi
    • 1
  • Yoshiaki Ogawa
    • 1
  • Hiroshi Kawada
    • 1
    • 2
  • Kiyoshi Ando
    • 1
    • 2
  1. 1.Division of Hematology/Oncology, Department of Internal MedicineTokai University School of MedicineIseharaJapan
  2. 2.Research Center for Cancer Stem CellTokai University School of MedicineIseharaJapan
  3. 3.Department of laboratory MedicineTokai University School of MedicineIseharaJapan

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