Clinical significance of CADM1/TSLC1/IgSF4 expression in adult T-cell leukemia/lymphoma

Abstract

Cell adhesion molecule 1 (CADM1/TSLC1) was recently identified as a novel cell surface marker for adult T-cell leukemia/ lymphoma (ATLL). In this study, we developed various antibodies as diagnostic tools to identify CADM1-positive ATLL leukemia cells. In flow cytometric analysis, the percentages of CD4 þ CADM1 þ double-positive cells correlated well with both the percentages of CD4 þ CD25 þ cells and with abnormal lymphocytes in the peripheral blood of patients with various types of ATLL. Moreover, the degree of CD4 þ CADM1 þ cells over 1% significantly correlated with the copy number of the human T-lymphotropic virus type 1 (HTLV-1) provirus in the peripheral blood of HTLV-1 carriers and ATLL patients. We also identified a soluble form of CADM1 in the peripheral blood of ATLL patients, and the expression levels of this form were correlated with the levels of soluble interleukin 2 receptor alpha. Moreover, lymphomas derived from ATLL were strongly and specifically stained with a CADM1 antibody. Thus, detection of CD4 þ CADM1 þ cells in the peripheral blood, measurement of serum levels of soluble CADM1 and immunohistochemical detection of CADM1 in lymphomas would be a useful set of markers for disease progression in ATLL and may aid in both the early diagnosis and measurement of treatment efficacy for ATLL.

Tumor Suppressor in Lung Cancer-1 Is a Prognostic Predictor for the Recurrence and Progression of Non-Muscle-Invasive Bladder Cancer

“…Our results showed that TSLC1 expression was low in NMIBC tissues, in agreement with the reported low expression of TSLC1 in other tumors [10,11,12,13,14,15,16,17,18,19,20,21]. The function of TSLC1 is to participate in calcium-independent cell-cell adhesion and signal transduction, similar to E-cadherin [7].…”

“…Previous studies have shown that TSLC1 is ubiquitously expressed in a wide range of human tissues, such as the lung, brain, testes as well as most epithelial and neuronal tissues [9]. Recently, TSLC1 protein expression was found to be lost or downregulated in a variety of human cancers, including lung, breast, nasopharyngeal, cervical, liver and colon cancer, meningioma, cutaneous melanoma and T-cell leukemia/lymphoma [10,11,12,13,14,15,16,17,18,19,20,21]. Furthermore, experimental studies have shown that reconstitution of TSLC1 expression inhibited esophageal carcinoma in vitro and in vivo [22,23,24].…”

CADM1 Expression and Stepwise Downregulation of CD7 Are Closely Associated with Clonal Expansion of HTLV-I–Infected Cells in Adult T-cell Leukemia/Lymphoma

“…þ cells have been found to be significantly correlated with the proviral load (PVL) in both ATLs and HTLV-I asymptomatic carriers (25,27). Thus, CADM1 is a good candidate marker of HTLV-I-infected cells.…”

“…On the basis of previous reports (25,27), we expected HTLV-I-infected cells to be enriched in the CADM1 þ subpopulations in our analysis. Figure 2A shows the PVL measurements of the three subpopulations in the CADM1 versus CD7 plot for three representative cases.…”

Establishment of a novel human lymphoblastic cell strain with the long arm of chromosome 11 aberration without MLL rearrangement

“…Knowing that cells that can be monoclonally cultured and derived from tumors formed by CHH-1 cells also contain the same cytogenetic aberration, we speculate that the tumorigenicity of CHH-1 cells may be associated with this cytogenetic abnormality. Except MLL , there are many other proto-oncogenes and tumor suppressor genes such as ETS1 27 , FLI1 28 , LARG 29 , CADM1 30 , DDX6 31 , PLZF 32 , TSG11 and THY1 that are located between 11q23 and 11q25. In addition, the break in and the additional material on the long arm of chromosome 11 may create various genetic aberrations including new translocation, amplification and deletion.…”