Clinical significance of soluble CADM1 as a novel marker for adult T-cell leukemia/lymphoma.


Nakahata S(1), Syahrul C(1), Nakatake A(1), Sakamoto K(1), Yoshihama M(1), Nishikata I(1), Ukai Y(2), Matsuura T(2), Kameda T(3), Shide K(3), Kubuki Y(3), Hidaka T(3), Kitanaka A(4), Ito A(5), Takemoto S(6), Nakano N(7), Saito M(8), Iwanaga M(9), Sagara Y(10), Mochida K(11), Amano M(11), Maeda K(12), Sueoka E(13), Okayama A(14), Utsunomiya A(7), Shimoda K(3), Watanabe T(15), Morishita K(1).
Author information:
(1)Department of Medical Sciences, University of Miyazaki, Miyazaki, Japan.
(2)Perseus Proteomics Inc., Tokyo, Japan.
(3)Department of Internal Medicine, University of Miyazaki, Miyazaki, Japan.
(4)Department of Laboratory Medicine, Kawasaki Medical School, Okayama, Japan.
(5)Department of Pathology, Kindai University School of Medicine, Osaka, Japan.
(6)National Hospital Organization Kumamoto Medical Center, Kumamoto, Japan.
(7)Department of Hematology, Imamura General Hospital, Kagoshima, Japan.
(8)National Institute of Infectious Diseases, Tokyo, Japan.
(9)Dept of Frontier Life Science, Nagasaki University Graduate School of Biomedical Sciences, Japan.
(10)Japanese Red Cross Kyushu Block Blood Center, Fukuoka, Japan.
(11)Department of Dermatology, Faculty of Medicine, University of Miyazaki, Miyazaki, Japan.
(12)Internal Medicine, National Hospital Organization Miyakonojo Medical Center, Miyazaki, Japan.
(13)Department of Laboratory Medicine, Saga University Hospital, Saga, Japan.
(14)Dept. of Infectious Diseases and Laboratory Medicine, University of Miyazaki, Miyazaki, Japan.
(15)Department of Computational Biology and Medical Sciences, University of Tokyo, Japan.


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 have recently shown that cell adhesion molecule 1 (CADM1), a member of the immunoglobulin superfamily, 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 showed that plasma sCADM1 concentrations 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, a measurement of sCADM1 may become a useful tool to discriminate between ATLL and other inflammatory diseases, including HAM/TSP.