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

Ryujiro Hara1, Makoto Onizuka2,3, Erika Matsusita1

  • 1Division of Hematology/Oncology, Department of Internal Medicine, Tokai University School of Medicine, 143 Shimokasuya, Isehara, Kanagawa, 259-1143, Japan.

International Journal of Hematology
|August 11, 2017
PubMed

Insights

Natural killer (NK) cell gene polymorphisms may predict treatment-free remission in chronic myeloid leukemia (CML) patients receiving dasatinib. Specific NKG2D gene variations correlate with faster achievement of deep molecular remission, suggesting their potential as biomarkers.

Area of Science:

  • Immunogenetics
  • Hematology
  • Oncology

Background:

  • Treatment-free remission (TFR) in chronic myeloid leukemia (CML) after dasatinib (Das) treatment is linked to natural killer (NK) cell activity.
  • Biomarkers for predicting lymphocytosis or successful TFR remain poorly defined.

Purpose of the Study:

  • To investigate the association between polymorphisms in the natural killer group 2D receptor (NKG2D) gene and clinical outcomes in CML patients treated with dasatinib.
  • To explore individual differences in NK cell responses to dasatinib based on genetic variations.

Main Methods:

  • Retrospective analysis of 31 CML patients treated with first-line dasatinib.
  • Association study of NKG2D (KLRK1) gene polymorphisms with clinical outcomes, including time to MR4.5.
  • Analysis of NK cell phosphorylation in relation to NKG2D alleles.

Main Results:

  • Patients with the NKG2D HNK1/HNK1 haplotype achieved MR4.5 significantly faster than other haplotypes (HR 4.39, P=0.004).
  • NK cells expressing the NKG2D HNK1 allele showed enhanced VAV1 phosphorylation at Tyr174.
  • NKG2D gene polymorphisms were associated with faster remission achievement.

Conclusions:

  • NKG2D gene polymorphisms may serve as predictive biomarkers for TFR in CML patients undergoing dasatinib therapy.
  • The HNK1 allele of NKG2D is associated with improved clinical outcomes and enhanced NK cell function.
Keywords:
Chronic myeloid leukemiaNatural killer cellNatural killer group 2D receptorSingle nucleotide polymorphismVav guanine nucleotide exchange factor 1

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