CXorf48 is a potential therapeutic target for achieving treatment-free remission in CML patients

Maiko Matsushita, K. Ozawa, Takeshi Suzuki, M. Nakamura, N. Nakano, S. Kanchi, Daijyu Ichikawa, E. Matsuki, Masatoshi Sakurai, D. Karigane, H. Kasahara, Nobuo Tsukamoto, Takayuki Shimizu, Takehiko Mori, H. Nakajima, Shinichiro Okamoto, Yutaka Kawakami, Yutaka Hattori

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Abstract

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.

Original languageEnglish
Article numbere601
JournalBlood Cancer Journal
Volume7
Issue number9
DOIs
Publication statusPublished - 2017 Sep 1

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Leukemia, Myelogenous, Chronic, BCR-ABL Positive
Protein-Tyrosine Kinases
Stem Cells
Therapeutics
T-Lymphocytes
Recurrence
T-Lymphocyte Epitopes
Bone Marrow Cells
Immunotherapy
Immune System
Immunity
Blood Cells
Peptides
Survival

ASJC Scopus subject areas

  • Hematology
  • Oncology

Cite this

CXorf48 is a potential therapeutic target for achieving treatment-free remission in CML patients. / Matsushita, Maiko; Ozawa, K.; Suzuki, Takeshi; Nakamura, M.; Nakano, N.; Kanchi, S.; Ichikawa, Daijyu; Matsuki, E.; Sakurai, Masatoshi; Karigane, D.; Kasahara, H.; Tsukamoto, Nobuo; Shimizu, Takayuki; Mori, Takehiko; Nakajima, H.; Okamoto, Shinichiro; Kawakami, Yutaka; Hattori, Yutaka.

In: Blood Cancer Journal, Vol. 7, No. 9, e601, 01.09.2017.

Research output: Contribution to journalArticle

Matsushita, Maiko ; Ozawa, K. ; Suzuki, Takeshi ; Nakamura, M. ; Nakano, N. ; Kanchi, S. ; Ichikawa, Daijyu ; Matsuki, E. ; Sakurai, Masatoshi ; Karigane, D. ; Kasahara, H. ; Tsukamoto, Nobuo ; Shimizu, Takayuki ; Mori, Takehiko ; Nakajima, H. ; Okamoto, Shinichiro ; Kawakami, Yutaka ; Hattori, Yutaka. / CXorf48 is a potential therapeutic target for achieving treatment-free remission in CML patients. In: Blood Cancer Journal. 2017 ; Vol. 7, No. 9.
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AU - Nakano, N.

AU - Kanchi, S.

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AU - Shimizu, Takayuki

AU - Mori, Takehiko

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