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Profiles of NK cell subsets are associated with successful tyrosine kinase inhibitor discontinuation in chronic myeloid leukemia and changes following interferon treatment

Abstract

Recent studies have shown that approximately 50% of patients with chronic myeloid leukemia (CML) receiving tyrosine kinase inhibitor (TKI) therapy with a sustained deep molecular response (DMR) (BCR-ABL1IS ≤ 0.01%) can achieve treatment-free remission (TFR, stopping TKI without relapse) and that prior interferon (IFN)-α therapy and higher NK cell counts at and after TKI discontinuation are associated with TFR. We recently reported that post-TKI discontinuation of IFN-α therapy could prevent molecular relapse (MR, BCR-ABL1IS > 0.1%). Here, we evaluated whether NK cells are associated with MR and investigated the effects of post-TKI discontinuation IFN-α therapy on lymphocyte subsets. A total of 34 patients measuring blood lymphocyte subclasses were included. In the 22 patients who did not receive IFN-α therapy, at 1 month after TKI discontinuation, the nonrelapsed patients showed a significantly higher proportion and count of NK cells than the relapsed patients. In particular, the proportion and count of CD56dim NK cells were significantly higher in the nonrelapsed patients than in the relapsed patients. In the 12 patients who received IFN-α therapy, the level of CD56bright NK cells increased significantly after 3 and 6 months of IFN-α therapy. In summary, NK cells, in particular CD56dim NK cells, were associated with MR after TKI discontinuation in patients with CML. Additionally, IFN-α therapy gradually increased the level of CD56bright NK cells in patients with CML.

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Acknowledgements

The authors thank the faculty members who helped with this study.

Funding

This work was supported by the Capital Characteristic Clinic Project Foundation (Z181100001718126).

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Contributions

Jun Kong and Hao Jiang designed the study, and Jun Kong analyzed and interpreted the data and wrote the manuscript. Ya-zhen Qin and Xiao-su Zhao performed the RT-qPCR and FCM experiments.

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Correspondence to Hao Jiang.

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Kong, J., Qin, Yz., Zhao, XS. et al. Profiles of NK cell subsets are associated with successful tyrosine kinase inhibitor discontinuation in chronic myeloid leukemia and changes following interferon treatment. Ann Hematol 100, 2557–2566 (2021). https://doi.org/10.1007/s00277-021-04606-9

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  • DOI: https://doi.org/10.1007/s00277-021-04606-9

Keywords

  • Chronic myeloid leukemia
  • Tyrosine kinase inhibitor
  • Treatment-free remission
  • Natural killer cell
  • Interferon