TY - JOUR
T1 - CXorf48 is a potential therapeutic target for achieving treatment-free remission in CML patients
AU - Matsushita, M.
AU - Ozawa, K.
AU - Suzuki, T.
AU - Nakamura, M.
AU - Nakano, N.
AU - Kanchi, S.
AU - Ichikawa, D.
AU - Matsuki, E.
AU - Sakurai, M.
AU - Karigane, D.
AU - Kasahara, H.
AU - Tsukamoto, N.
AU - Shimizu, T.
AU - Mori, T.
AU - Nakajima, H.
AU - Okamoto, S.
AU - Kawakami, Y.
AU - Hattori, Y.
N1 - Funding Information:
We thank staffs of the Core Instrumentation Facility, Keio University School of Medicine for technical assistance. This work was supported by a Grant-in-Aid for Scientific Research and a grant from the Private University Strategic Research Base Development Program of the Ministry of Education, Culture, Sports, Science and Technology (MEXT) of Japan, Friends of Leukemia Research Fund, Encouragement Prize from Japanese Society of Myeloma and Keio Gijuku Academic Development Funds.
Publisher Copyright:
© 2017 The Author(s).
PY - 2017/9/1
Y1 - 2017/9/1
N2 - Although the introduction of tyrosine kinase inhibitors (TKIs) has improved overall survival of patients with chronic myeloid leukemia (CML), about half of the patients eventually relapse after cessation of TKIs. In contrast, the remainder of the patients maintain molecular remission without TKIs, indicating that the patients' immune system could control proliferation of TKI-resistant leukemic stem cells (LSCs). However, the precise mechanism of immunity against CML-LSCs is not fully understood. We have identified a novel immune target, CXorf48, expressed in LSCs of CML patients. Cytotoxic T cells (CTLs) induced by the epitope peptide derived from CXorf48 recognized CD34 + CD38 â' cells obtained from the bone marrow of CML patients. We detected CXorf48-specific CTLs in the peripheral blood mononuclear cells from CML patients who have discontinued imatinib after maintaining complete molecular remission for more than 2 years. Significantly, the relapse rate of CXorf48-specific CTL-negative patients was 63.6%, compared to 0% in CXorf48-specific CTL-positive patients. These results indicate that CXorf48 could be a promising therapeutic target of LSCs for immunotherapy to obtain durable treatment-free remission in CML patients.
AB - Although the introduction of tyrosine kinase inhibitors (TKIs) has improved overall survival of patients with chronic myeloid leukemia (CML), about half of the patients eventually relapse after cessation of TKIs. In contrast, the remainder of the patients maintain molecular remission without TKIs, indicating that the patients' immune system could control proliferation of TKI-resistant leukemic stem cells (LSCs). However, the precise mechanism of immunity against CML-LSCs is not fully understood. We have identified a novel immune target, CXorf48, expressed in LSCs of CML patients. Cytotoxic T cells (CTLs) induced by the epitope peptide derived from CXorf48 recognized CD34 + CD38 â' cells obtained from the bone marrow of CML patients. We detected CXorf48-specific CTLs in the peripheral blood mononuclear cells from CML patients who have discontinued imatinib after maintaining complete molecular remission for more than 2 years. Significantly, the relapse rate of CXorf48-specific CTL-negative patients was 63.6%, compared to 0% in CXorf48-specific CTL-positive patients. These results indicate that CXorf48 could be a promising therapeutic target of LSCs for immunotherapy to obtain durable treatment-free remission in CML patients.
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U2 - 10.1038/bcj.2017.84
DO - 10.1038/bcj.2017.84
M3 - Article
C2 - 28862699
AN - SCOPUS:85028680625
SN - 2044-5385
VL - 7
JO - Blood cancer journal
JF - Blood cancer journal
IS - 9
M1 - e601
ER -