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CXorf48 is a potential therapeutic target for achieving treatment-free remission in CML patients
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CXorf48 is a potential therapeutic target for achieving treatment-free remission in CML patients
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Journal Article
CXorf48 is a potential therapeutic target for achieving treatment-free remission in CML patients
2017
Overview
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
−
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.
Publisher
Nature Publishing Group UK,Springer Nature B.V,Nature Publishing Group
Subject
/ Biomedical and Life Sciences
/ Bone Marrow Cells - immunology
/ Bone Marrow Cells - pathology
/ CD8-Positive T-Lymphocytes - immunology
/ CD8-Positive T-Lymphocytes - pathology
/ Drugs
/ Female
/ Gene Expression Regulation, Leukemic - drug effects
/ Gene Expression Regulation, Leukemic - immunology
/ Humans
/ Leukemia, Myelogenous, Chronic, BCR-ABL Positive - drug therapy
/ Leukemia, Myelogenous, Chronic, BCR-ABL Positive - immunology
/ Leukemia, Myelogenous, Chronic, BCR-ABL Positive - pathology
/ Male
/ Neoplasm Proteins - immunology
/ Neoplastic Stem Cells - immunology
/ Neoplastic Stem Cells - pathology
/ Oncology
/ Original
