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Leukemia Stem Cells as a Potential Target to Achieve Therapy-Free Remission in Chronic Myeloid Leukemia

Regulatory T Cell as a Biomarker of Treatment-Free Remission in Patients with Chronic Myeloid Leukemia

Department of Hematology, Nephrology and Rheumatology, Akita University Graduate School of Medicine, 1-1-1 Hondo, Akita 010-8543, Japan
Division of Cancer Immunology, Exploratory Oncology Research and Clinical Trial Center (EPOC), National Cancer Center, Chiba 277-8577, Japan
Department of Immunology, Nagoya University Graduate School of Medicine, Nagoya 466-8550, Japan
Department of Hematology and Oncology, Kinki University Hospital, Osaka 589-8511, Japan
Department of Hematology, National Cancer Center Hospital East, Kashiwa 277-0882, Japan
Department of Pharmacy, Akita University Hospital, Akita 010-8543, Japan
The Japanese Data Center for Hematopoietic Cell Transplantation, Nagoya 461-0047, Japan
Kanazawa University, Kanazawa 920-1192, Japan
Department of Hematology and Oncology, Nagoya University, Nagoya 464-8601, Japan
Department of Hematology, Nagasaki University, Nagasaki 852-8521, Japan
Division of Cancer Immunology, Research Institute, National Cancer Center, Tokyo 104-0045, Japan
Authors to whom correspondence should be addressed.
Academic Editors: Francesca Romana Mauro and François Guilhot
Cancers 2021, 13(23), 5904;
Received: 3 October 2021 / Revised: 2 November 2021 / Accepted: 15 November 2021 / Published: 24 November 2021
(This article belongs to the Special Issue Molecular Genetics and Treatment of Chronic Myeloid Leukemia)
Tyrosine kinase inhibitors (TKIs) have dramatically improved the treatment of chronic myeloid leukemia (CML). Recently, TKIs were discontinued in patients with CML with deep molecular remission, and some patients have been reported to be able to maintain long-term treatment-free remission (TFR). However, there is no certainty regarding which patients can maintain TFR. We focused on immunity in the TFR phase and investigated the immunological mechanism of continuous TFR or recurrence. Our results suggest that the group that maintains the TFR is immunologically activated. In addition, regulatory T cells can be used as a biomarker. These results may have important implications for future strategies for maintaining TFR in CML treatment.
Treatment-free remission (TFR) has become a therapeutic goal in chronic myeloid leukemia (CML), and approximately half of the patients with chronic phase-CML (CML-CP) with deep molecular remission (DMR) by tyrosine-kinase inhibitors (TKIs) have achieved TFR. However, the mechanism of continuous TFR is still unclear, as there are “fluctuate” patients who have BCR–ABL-positive leukemia cells but do not observe obvious relapse. We focused on the immune response and conducted an immune analysis using clinical samples from the imatinib discontinuation study, JALSG-STIM213. The results showed that, in the group that maintained TFR for 3 years, changes in regulatory T (Treg) cells were observed early after stopping imatinib treatment. The effector Treg (eTreg) cells increased transiently at 1 month after stopping imatinib and then returned to baseline at 3 months after stopping imatinib treatment. There was no difference in the Treg phenotype, and CD8+ T cells in the TFR group were relatively activated. High concentrations of imatinib before stopping were negatively correlated with eTreg cells after stopping imatinib. These data suggest immunological involvement in the maintenance of the TFR, and that Treg cells after stopping imatinib might be a biomarker for TFR. Furthermore, high imatinib exposure may have a negative immunological impact on the continuous TFR. View Full-Text
Keywords: chronic myeloid leukemia; imatinib; treatment-free remission; regulatory T cells chronic myeloid leukemia; imatinib; treatment-free remission; regulatory T cells
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MDPI and ACS Style

Fujioka, Y.; Sugiyama, D.; Matsumura, I.; Minami, Y.; Miura, M.; Atsuta, Y.; Ohtake, S.; Kiyoi, H.; Miyazaki, Y.; Nishikawa, H.; Takahashi, N. Regulatory T Cell as a Biomarker of Treatment-Free Remission in Patients with Chronic Myeloid Leukemia. Cancers 2021, 13, 5904.

AMA Style

Fujioka Y, Sugiyama D, Matsumura I, Minami Y, Miura M, Atsuta Y, Ohtake S, Kiyoi H, Miyazaki Y, Nishikawa H, Takahashi N. Regulatory T Cell as a Biomarker of Treatment-Free Remission in Patients with Chronic Myeloid Leukemia. Cancers. 2021; 13(23):5904.

Chicago/Turabian Style

Fujioka, Yuki, Daisuke Sugiyama, Itaru Matsumura, Yosuke Minami, Masatomo Miura, Yoshiko Atsuta, Shigeki Ohtake, Hitoshi Kiyoi, Yasushi Miyazaki, Hiroyoshi Nishikawa, and Naoto Takahashi. 2021. "Regulatory T Cell as a Biomarker of Treatment-Free Remission in Patients with Chronic Myeloid Leukemia" Cancers 13, no. 23: 5904.

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