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Molecular Cancer Therapeutics
Molecular Cancer Therapeutics
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Companion Diagnostic, Pharmacogenomic, and Cancer Biomarkers

HLA Polymorphisms Are Associated with Treatment-Free Remission Following Discontinuation of Tyrosine Kinase Inhibitors in Chronic Myeloid Leukemia

Hiroshi Ureshino, Takero Shindo, Hidenori Tanaka, Hiroh Saji and Shinya Kimura
Hiroshi Ureshino
1Division of Hematology, Respiratory Medicine and Oncology, Department of Internal Medicine, Saga University, Saga, Japan.
2Department of Drug Discovery and Biomedical Sciences, Saga University, Saga, Japan.
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  • For correspondence: sr0795@cc-saga-u.ac.jp
Takero Shindo
3Department of Hematology and Oncology, Kyoto University Graduate School of Medicine, Kyoto, Japan.
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Hidenori Tanaka
4HLA Foundation Laboratory, Kyoto, Japan.
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Hiroh Saji
4HLA Foundation Laboratory, Kyoto, Japan.
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Shinya Kimura
1Division of Hematology, Respiratory Medicine and Oncology, Department of Internal Medicine, Saga University, Saga, Japan.
2Department of Drug Discovery and Biomedical Sciences, Saga University, Saga, Japan.
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DOI: 10.1158/1535-7163.MCT-20-0336 Published January 2021
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Abstract

Treatment-free remission (TFR) is one of the therapeutic goals for patients with chronic phase chronic myeloid leukemia (CML-CP). Although previous reports indicated that antitumor immunity contributes to TFR, its determinants are still unclear. We previously reported that allelic polymorphisms of killer immunoglobulin-like receptors (KIR) and human leukocyte antigens (HLA) are associated with achievement of deep molecular response (DMR) in patients with CML-CP. Here, we examined the association between TFR and polymorphisms of KIRs and HLAs in patients who discontinued tyrosine kinase inhibitors (TKI). Seventy-six patients were enrolled, and their KIR and HLA polymorphisms and natural killer (NK) cell activation status were investigated as previously described. Overall, 33 patients discontinued TKIs, and 21 of 33 achieved TFR [63.6%; 95% confidence interval (CI), 44.9%–77.5%] at 1 year. Multivariate analysis revealed that male sex (HR, 0.157; 95% CI, 0.031–0.804; P = 0.003) and HLA-A*02:01, *11:01, or *24:02 (HR, 6.386; 95% CI, 1.701–23.980; P = 0.006) were associated with TFR. Patients who achieved DMR and discontinued TKIs exhibited higher NK cell activation status than those who did not. By contrast, there were no significant differences in NK cell activation status between the patients who achieved TFR and those who experienced molecular relapse. These results suggest NK cell activation status contributes to achievement of DMR, whereas T-cell–mediated immunity contributes to TFR in patients with CML-CP.

This article is featured in Highlights of This Issue, p. 1

Footnotes

  • Note: Supplementary data for this article are available at Molecular Cancer Therapeutics Online (http://mct.aacrjournals.org/).

  • Mol Cancer Ther 2021;20:142–9

  • Received April 27, 2020.
  • Revision received August 31, 2020.
  • Accepted October 6, 2020.
  • Published first October 20, 2020.
  • ©2020 American Association for Cancer Research.
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Molecular Cancer Therapeutics: 20 (1)
January 2021
Volume 20, Issue 1
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HLA Polymorphisms Are Associated with Treatment-Free Remission Following Discontinuation of Tyrosine Kinase Inhibitors in Chronic Myeloid Leukemia
Hiroshi Ureshino, Takero Shindo, Hidenori Tanaka, Hiroh Saji and Shinya Kimura
Mol Cancer Ther January 1 2021 (20) (1) 142-149; DOI: 10.1158/1535-7163.MCT-20-0336

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HLA Polymorphisms Are Associated with Treatment-Free Remission Following Discontinuation of Tyrosine Kinase Inhibitors in Chronic Myeloid Leukemia
Hiroshi Ureshino, Takero Shindo, Hidenori Tanaka, Hiroh Saji and Shinya Kimura
Mol Cancer Ther January 1 2021 (20) (1) 142-149; DOI: 10.1158/1535-7163.MCT-20-0336
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Molecular Cancer Therapeutics
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