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Ferrata Storti Foundation
Acute Lymphoblastic Leukemia
Clinical significance of soluble CADM1 as a novel marker for adult T-cell leukemia/lymphoma
Haematologica 2021 Volume 106(2):532-542
11 12 13 14 Masahiro Amano, Kouichi Maeda, Eisaburo Sueoka, Akihiko Okayama,
Shingo Nakahata,1* Syahrul Chilmi,1* Ayako Nakatake,1 Kuniyo Sakamoto,1
Maki Yoshihama,1 Ichiro Nishikata,1 Yoshinori Ukai,2 Tadashi Matsuura,2
Takuro Kameda,3 Kotaro Shide,3 Yoko Kubuki,3 Tomonori Hidaka,3
Akira Kitanaka,4 Akihiko Ito,5 Shigeki Takemoto,6° Nobuaki Nakano,7
Masumichi Saito,8 Masako Iwanaga,9 Yasuko Sagara,10 Kosuke Mochida,11
7 3 15 Atae Utsunomiya, Kazuya Shimoda, Toshiki Watanabe
and Kazuhiro Morishita1
1Division of Tumor and Cellular Biochemistry, Department of Medical Sciences, Faculty of Medicine, University of Miyazaki, Miyazaki; 2Perseus Proteomics Inc., Perseus Proteomics Inc., Tokyo; 3Division of Gastroenterology and Hematology, Department of Internal Medicine, Faculty of Medicine, University of Miyazaki, Miyazaki; 4Department of Laboratory Medicine, Kawasaki Medical School, Okayama; 5Department of Pathology, Kindai University School of Medicine, Osaka; 6National Hospital Organization Kumamoto Medical Center, Kumamoto; 7Department of Hematology, Imamura General Hospital, Kagoshima, 8Department of Safety Research on Blood and Biological Products, National Institute of Infectious Diseases, Tokyo; 9Department of Frontier Life Science, Nagasaki University Graduate School of Biomedical Sciences, Nagasaki; 10Japanese Red Cross Kyushu Block Blood Center, Fukuoka; 11Department of Dermatology, Faculty of Medicine, University of Miyazaki, Miyazaki; 12Internal Medicine, National Hospital Organization Miyakonojo Medical Center, Miyazaki; 13Department of Laboratory Medicine, Saga University Hospital and Department of Clinical Laboratory Medicine, Faculty of Medicine, Saga University, Saga; 14Department of Rheumatology, Infectious Diseases and Laboratory Medicine, University of Miyazaki, Miyazaki and 15Department of Computational Biology and Medical Sciences, Graduate School of Frontier Sciences, The University of Tokyo, Tokyo, Japan
*SN and CS contributed equally as co-first authors.
°Current address: JURAKU Internal Medicine Clinic, Kumamoto, Japan.
ABSTRACT
Adult T-cell leukemia/leukemia (ATLL) is an aggressive peripheral T-cell malignancy, caused by infection with the human T-cell leukemia virus type 1 (HTLV-1). We recently showed that the cell adhesion molecule 1 (CADM1), a member of the immunoglobulin super- family, is specifically and consistently overexpressed in ATLL cells, and functions as a novel cell surface marker. In this study, we first show that a soluble form of CADM1 (sCADM1) is secreted from ATLL cells by mainly alternative splicing. After developing the Alpha linked immunosorbent assay (AlphaLISA) for sCADM1, we show that plasma sCADM1 concen- trations gradually increased during disease progression from indolent to aggressive ATLL. Although other known biomarkers of tumor burden such as soluble interleukin-2 receptor α (sIL-2Rα) also increased with sCADM1 during ATLL progression, multivariate statistical analysis of biomarkers revealed that only plasma sCADM1 was selected as a specific biomarker for aggressive ATLL, suggesting that plasma sCADM1 may be a potential risk factor for aggressive ATLL. In addition, plasma sCADM1 is a useful marker for monitoring response to chemotherapy as well as for predicting relapse of ATLL. Furthermore, the change in sCADM1 concentration between indolent and aggressive type ATLL was more prominent than the change in the percentage of CD4+CADM1+ ATLL cells. As plasma sCADM1 values fell within normal ranges in HTLV-1-associated myelopathy/tropical spastic paraparesis (HAM/TSP) patients with higher levels of serum sIL-2Rα, the measurement of sCADM1 may become a useful tool to discriminate between ATLL and other inflammatory diseases, including HAM/TSP.
Correspondence:
KAZUHIRO MORISHITA
kmorishi@med.miyazaki-u.ac.jp
Received: August 21, 2019. Accepted: February 7, 2020. Pre-published: February 13, 2020.
https://doi.org/10.3324/haematol.2019.234096
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