Overexpression of a cell adhesion molecule, TSLC1, as a possible molecular marker for acute-type adult T-cell leukemia

Sasaki, Hidetada; Nishikata, Ichiro; Shiraga, Toshiyuki; Akamatsu, Ena; Fukami, Takeshi; Hidaka, Tomonori; Kubuki, Yoko; Okayama, Akira; Hamada, Kenji; Okabe, Hisafumi; Murakami, Yoshinori; Tsubouchi, Hirohito; Morishita, Kazuhiro

doi:10.1182/blood-2004-03-1222

Cited by 167 publications

(171 citation statements)

References 33 publications

(38 reference statements)

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“…17 We first analyzed the CADM1 protein levels in a panel of T-leukemia cell lines using a chicken anti-human CADM1 antibody (MBL, Nagoya, Japan). A 107 kDa band was clearly detected in whole-cell lysates from the KOB, KK1 and S1T cell lines (Figure 1a), which have been reported to express CADM1 according to reverse transcriptase PCR and northern blot analysis.…”

Section: Resultsmentioning

confidence: 99%

“…A 107 kDa band was clearly detected in whole-cell lysates from the KOB, KK1 and S1T cell lines (Figure 1a), which have been reported to express CADM1 according to reverse transcriptase PCR and northern blot analysis. 17 To confirm CADM1 expression on the cell surface of ATLL cells, we examined CADM1 membrane expression by flow cytometry with an Alexa 488-labeled human anti-CADM1 antibody generated by phage-display technology. 22 Four ATLL cell lines were used for flow cytometry: CADM1-negative ED and CADM1-positive KOB, KK1 and S1T cell lines.…”

Section: Resultsmentioning

confidence: 99%

“…In all three CADM1-positive cell lines, the fluorescence intensity of CADM1 expression was two logs greater than that of the isotype immunoglobulin G control (Figure 1b, upper panels), while only background levels of fluorescence could be seen in the CADM1-negative ED-ATLL cell line, which had high levels of DNA methylation in the CADM1 promoter region. 17 To evaluate the subcellular distribution of CADM1, immunohistochemical staining was performed on the same cell lines using the anti-CADM1 antibody (Figure 1b, bottom panels). CADM1 was highly concentrated at the cell --cell contact sites in the three CADM1-positive cell lines, and no staining of CADM1 was detected in the ED cell line.…”

Section: Resultsmentioning

confidence: 99%

“…As positive controls, we used erythrocytes and peripheral nerve tissue (Figure 5a, panels 3 and 4). 17,18 In addition, we examined CADM1 Figure 3. Correlation of the percentages of the CD4 þ CADM1 þ fraction with the percentages of abnormal lymphocytes, HTLV-1 DNA copy number and the levels of soluble IL-2Ra and serum LDH in both various types of patients with ATLL and HTLV-1 carriers.…”

Section: Resultsmentioning

confidence: 99%

“…Using a comprehensive DNA microarray gene expression analysis, we recently demonstrated that cell adhesion molecule 1 (CADM1/TSLC1/IgSF4) is a novel cell surface maker for ATLL. 17 CADM1 was initially isolated as a tumor suppressor for lung cancers by genomic analysis. CADM1 expression is reduced in a variety of cancers by promoter methylation and is associated with poor prognosis and enhanced metastatic potential.…”

Section: Introductionmentioning

confidence: 99%

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

et al. 2012

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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.

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Section: Resultsmentioning

confidence: 99%

Section: Resultsmentioning

confidence: 99%

Section: Resultsmentioning

confidence: 99%

Section: Resultsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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

et al. 2012

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Molecular Classification of the Peripheral T‐cell Lymphomas

Herek

Iqbal

2021

The Peripheral T‐Cell Lymphomas

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Alteration of enhancer of polycomb 1 at 10p11.2 is one of the genetic events leading to development of adult T‐cell leukemia/lymphoma

Nakahata

Saito

Hamasaki

et al. 2009

Genes Chromosomes & Cancer

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Adult T-cell leukemia/lymphoma (ATLL) is a malignant tumor caused by latent human T-lymphotropic virus 1 (HTLV-1) infection. We previously identified a common breakpoint cluster region at 10p11.2 in acute-type ATLL by spectral karyotyping. Single nucleotide polymorphism array comparative genomic hybridization analysis of the breakpoint region in three ATLL-related cell lines and four patient samples revealed that the chromosomal breakpoints are localized within the enhancer of polycomb 1 (EPC1) gene locus in an ATLL-derived cell line (SO4) and in one patient with acute-type ATLL. EPC1 is a human homologue of the E(Pc) enhancer of polycomb gene of Drosophila. Inappropriate expression of the polycomb group gene family has been linked to the loss of normal gene silencing pathways, which can contribute to the loss of cell identity and malignant transformation in many kinds of cancers. In the case of the SO4 cell line, which carried a der(10)t(2;10)(p23;p11.2) translocation, EPC1 was fused with the additional sex combs-like 2 (ASXL2) gene at 2p23.3 (EPC1/ASXL2). In the case with an acute-type ATLL, who carried a der(10)del(10)(p11.2)del(10)(q22q24) translocation, a putative truncated EPC1 gene (EPC1tr) was identified. Overexpression of EPC1/ASXL2 enhanced cell growth in T-leukemia cells, and a GAL4-EPC1/ASXL2 fusion protein showed high transcriptional activity. Although a GAL4-EPC1tr fusion protein did not activate transcription, overexpression of EPC1tr accelerated cell growth in leukemia cells, suggesting that the EPC1 structural abnormalities in the SO4 cell line and in the patient with acute-type ATLL may contribute to leukemogenesis.

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Overexpression of a cell adhesion molecule, TSLC1, as a possible molecular marker for acute-type adult T-cell leukemia

Cited by 167 publications

References 33 publications

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

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

Molecular Classification of the Peripheral T‐cell Lymphomas

Alteration of enhancer of polycomb 1 at 10p11.2 is one of the genetic events leading to development of adult T‐cell leukemia/lymphoma

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