Diagnostic Value of protocadherin 15 on NK/T Cell Lymphoma

Abstract Objective: NK/T cell lymphoma is a unique subtype of non-Hodgkin’s lymphoma, accounting for 5% to 15% of lymphomas, and shows a prediction for the crowd of Asia, central and South America. Nasal, nasopharynx and oropharynx regions are commonly involved. Lesions may also occur in the upper respiratory tract, gastrointestinal tract, testis and other parts. Diagnosis of NK/T cell lymphoma is dependent on the pathological study of lesion biopsy specimens. Nevertheless, poor quantity or quality of specimens, such as tissue extensive necrosis often become an obstacle to the early diagnosis. Therefore, investigating an easy sampling, accurate and stable experimental marker has profound clinical significance for the diagnosis of NK / T-cell lymphoma. Protocadherin15 (PCDH15) is a member of the cadherin family, which encoding gene located on chromosome 10q21-22. Rouget-Quermalet found a secreted isoform PCDH15 in the cracking sediment of human YT-type NK/T-cell lymphoma cell lines 8 years ago. PCDH15 was found not expressed in fresh or activated normal peripheral blood cells, CD4/CD8 positive lymphocytes, NK cells, normal spleen, lymph nodes, tonsils reactivity and CD34 + cord blood cells, only specifically expressed in three kinds of NK cell lymphoma cell lines. PCDH15 was not expressed in the biopsies of diffuse large B-cell lymphoma, mantle cell lymphoma and other types of lymphoma, but specifically expressed in NK/T lymphoma biopsy tissues. Since PCDH15-SI was found in the human NK/T-cell lymphoma cell lines, its relationship with NK / T-cell lymphoma as well as other types of lymphoma was rarely reported, and studies of clinical specimens are still blank. The purpose of this study is to investigate what whether the PCDH15 is specifically expressed in NK/T-cell lymphoma biopsies, and whether the PCDH15-SI, as a secreted isoform, is specifically present in peripheral serum of newly diagnosed NK/T-cell lymphoma or not. Materials and methods: 1. Screening biopsy paraffin blocks of NK/T-cell lymphoma(2010.1～2013.10) and non-NK/T-cell lymphoma(2012.10～2013.11) in West China Hospital of Sichuan University, which have 45cases and 33 cases stained by immunohistochemistry respectively and blank controls were set. 2. Collecting peripheral blood of NK/T-cell lymphoma, non-NK/T-cell lymphoma and normal population in the same Hospita. PCDH15 content of serum samples were detected by enzyme-linked immunosorbent content analysis (ELISA) method. Results: 1. Results of immunohistochemistry showed that PCDH15 were expressed both in the experimental group NK/T-cell lymphoma and the control group with non-NK/T cell lymphoma. High expression rate in the NK/T-cell lymphoma group was higher than in non-NK/T cell lymphoma. The differences of PCDH15 expression levels between the two groups, or among the different anatomical structures were not statistically significant (P > 0.05). 2. PCDH15-SI can be detected in peripheral blood in the normal population, the experimental group of NK/T-cell lymphoma as well as in the control group of non-NK/T-cell lymphoma, which the level of PCDH15-SI in those patients with newly diagnosed disease was higher than that of the normal population and the serum level in the non-NK/T-cell lymphoma patients was higher than that in the NK/T-cell lymphoma patients(P < 0.05). Conclusions: 1. PCDH15 was expressed in biopsies of different types of lymphoma, and the degree of expression in NK/T-cell lymphoma was significantly higher. 2. PCDH15 can’t be used to diagnose NK/T cell lymphoma as a marker. Disclosures No relevant conflicts of interest to declare.

Download Full-text

Peripheral blood neutrophil-to-lymphocyte ratio in NK/T-cell lymphoma - prognostic significance and correlation with tumor transcriptomic profiles

Annals of Oncology ◽

10.1093/annonc/mdy437.006 ◽

2018 ◽

Vol 29 ◽

pp. ix88-ix89

Author(s):

T. Khee Ming ◽

B. Chia ◽

J.Q. Lim ◽

L.P. Khoo ◽

C.L. Cheng ◽

...

Keyword(s):

T Cell ◽

Peripheral Blood ◽

Cell Lymphoma ◽

Prognostic Significance ◽

T Cell Lymphoma ◽

Neutrophil To Lymphocyte Ratio ◽

Blood Neutrophil ◽

Lymphocyte Ratio ◽

Peripheral Blood Neutrophil ◽

Nk T Cell

Download Full-text

Modification of extracorporeal photopheresis technology with porphyrin precursors. Comparison between 8-methoxypsoralen and hexaminolevulinate in killing human T-cell lymphoma cell lines in vitro

Biochimica et Biophysica Acta (BBA) - General Subjects ◽

10.1016/j.bbagen.2014.05.020 ◽

2014 ◽

Vol 1840 (9) ◽

pp. 2702-2708 ◽

Cited By ~ 8

Author(s):

B. Čunderlíková ◽

V. Vasovič ◽

L.L. Randeberg ◽

E. Christensen ◽

T. Warloe ◽

...

Keyword(s):

T Cell ◽

Cell Lines ◽

Cell Lymphoma ◽

T Cell Lymphoma ◽

Lymphoma Cell ◽

Extracorporeal Photopheresis ◽

Human T Cell

Download Full-text

Curcumin Selectively Induces Apoptosis in Cutaneous T-Cell Lymphoma Cell Lines and Patients’ PBMCs: Potential Role for STAT-3 and NF-κB Signaling

Journal of Investigative Dermatology ◽

10.1038/jid.2010.86 ◽

2010 ◽

Vol 130 (8) ◽

pp. 2110-2119 ◽

Cited By ~ 62

Author(s):

Chunlei Zhang ◽

Baoqiang Li ◽

Xiang Zhang ◽

Parul Hazarika ◽

Bharat B. Aggarwal ◽

...

Keyword(s):

T Cell ◽

Cell Lines ◽

Potential Role ◽

Cell Lymphoma ◽

T Cell Lymphoma ◽

Lymphoma Cell ◽

Cutaneous T Cell Lymphoma

Download Full-text

Anti-CD45 Mediated Cytolysis of Human T-Cell Lymphoma Cells.

Blood ◽

10.1182/blood.v104.11.4637.4637 ◽

2004 ◽

Vol 104 (11) ◽

pp. 4637-4637

Author(s):

Gerald G. Wulf ◽

Anita Boehnke ◽

Bertram Glass ◽

Lorenz Truemper

Keyword(s):

T Cell ◽

B Cell ◽

Cell Lines ◽

Cell Lymphoma ◽

B Cell Lymphoma ◽

Cytolytic Activity ◽

T Cell Lymphoma ◽

Lymphoma Cell ◽

Lymphoma Cells ◽

Human T Cell

Abstract Anti-CD45 mediated cytoreduction is an effective means for T-cell depletion in rodents and humans. In man, the CD45-specific rat monoclonal antibodies YTH24 and YTH54 are IgG2b subclass, exert a predominantly complement-dependent cytolytic activity against normal T-lymphocytes, and have been safely given to patients as part of conditioning therapies for allogeneic stem cell transplantation. The efficacy of such antibodies against human lymphoma is unknown. Therefore, we evaluated the cytolytic activity of YTH24 and YTH54 by complement-dependent cytotoxicity (CDC), antibody-dependent cell-mediated cytotoxicity (ADCC), as well as by direct apoptotic and antiproliferative effects, against a panel of Hodgkin disease (HD) and non-Hodgkin lymphoma (NHL) cell lines, and against primary specimens. Significant CDC activity (>50% cytolysis) of the antibodies YTH54 and YTH24 was observed against three of five T-cell lymphoma lines, but against only one of nine B-cell lymphoma lines and none of four HD cell lines. The combination of YTH54 and YTH24 induced ADCC in all T-cell lymphoma cell lines and three primary leukemic T-cell lymphoma specimens, but were ineffective in B-cell lymphoma and HD cell lines.There were only minor effects of either antibody or the combination on lymphoma cell apoptosis or cell cycle arrest. In summary, anti-CD45 mediated CDC and ADCC via the antibodies YTH24 and YTH54 are primarily effective against lymphoma cells with T-cell phenotype, and may be an immunotherapeutic tool for the treatment of human T-cell lymphoma.

Download Full-text

Characterization of T-Cell Lymphoma Cell Lines with a Novel t(9;14)(q34;q11.2) Rearrangement: Does gamma-Secretase Inhibitor Sensitivity Depend on Intragenic NOTCH1 Breakpoint?.

Blood ◽

10.1182/blood.v108.11.2332.2332 ◽

2006 ◽

Vol 108 (11) ◽

pp. 2332-2332

Author(s):

Shinsuke Suzuki ◽

Stefan Nagel ◽

Bjoern Schneider ◽

Maren Kaufmann ◽

Dorothea Anders ◽

...

Keyword(s):

T Cell ◽

Cell Line ◽

Cell Lines ◽

Cell Lymphoma ◽

T Cell Lymphoma ◽

Lymphoma Cell ◽

Gamma Secretase ◽

Secretase Inhibitor ◽

Gamma Secretase Inhibitor

Abstract Activating mutations and deletions affecting specific NOTCH1 protein domains have been recently shown to occur widely in T-cell neoplasia, e.g. in T-acute lymphoblastic leukemia (T-ALL). However, knowledge of NOTCH1 chromosomal alterations is largely based on a single cell line model (SUP-T1) with t(7;9)(q35;q34) in which NOTCH1 truncated at exon 24 is juxtaposed with TCRB. We describe the characterization of a novel rearrangement, t(9;14)(q34.3;q11) in two T-cell lymphoma cell lines, HD-MAR and HT-1. FISH analysis using fosmid clones and sequencing of fragments identified by long distance inverse PCR showed that in both cases t(9;14) effected tail-to-tail juxtaposition of intron 27 of NOTCH1 with TCRA genes, namely 5′-TRAV40 in HD-MAR, and intron 2 of TRAV5 in HT-1. Thus, in both cell lines t(9;14) places NOTCH1, truncated immediately 3′ of the HD-domain, under transcriptional control of TCRA. The 14q11.2 breakpoints in HD-MAR and HT-1 lie, respectively, near the proximal E-delta enhancer and amid a cryptic enhancer region represented by a cluster of T-cell specific DNase-I hypersensitive sites. Western blotting revealed prominent expression of truncated activated NOTCH1 polypeptides, ranging in size from 100 to 115 kDa in both cell lines. Antibodies recognizing ANK and TAD domains, believed essential for inducing T-ALL, detected the aberrant polypeptides. Moreover, treatment with gamma-secretase inhibitor (GSI) altered expression patterns of NOTCH1 polypeptides and induced growth inhibition due to G0/G1 cell cycle arrest in both t(9;14) cell lines, in stark contrast to GSI-resistant SUP-T1 cells wherein truncation occurs before the heterodimerization (HD) domain. (Another recently described t(7;9) cell line (CUTLL1) which is GSI-sensitive also carries a NOTCH1 breakpoint at intron 27.) The same protein species were not detectable by antibodies recognizing the transmembrane domain of NOTCH1 which requires GS for exposure suggesting nuclear access requires GS-cleavage. Immunostaining confirmed extranuclear blocking of NOTCH1 in response to GSI in HD-MAR/HT-1 but not in SUP-T1. In contrast, repression of HES1 occurred in response to GSI irrespective of NOTCH1 breakpoint location, suggesting its non-involvement in growth signaling. In addition to providing cell line models for a new NOTCH1 disease translocation, these data suggest that the sensitivities of T-cell neoplasias bearing NOTCH1 translocations may critically depend on whether 9q34 breakpoints lie upstream or downstream of the HD domain.

Download Full-text

The Role of Mir-150 as a Tumor Suppressor In Malignant Lymphoma

Blood ◽

10.1182/blood.v116.21.465.465 ◽

2010 ◽

Vol 116 (21) ◽

pp. 465-465

Author(s):

Atsushi Watanabe, ◽

Hiroyuki Tagawa ◽

Kazuaki Teshima ◽

Yoshihiro Kameoka ◽

Naoto Takahashi ◽

...

Keyword(s):

T Cell ◽

Tumor Suppressor ◽

Cell Lines ◽

Nk Cell ◽

Cell Lymphoma ◽

Telomerase Activity ◽

Akt Signaling ◽

T Cell Lymphoma ◽

Nk T Cell

Abstract Abstract 465 Disease specific genetic alteration or translocation have not been identified in NK/T cell lymphoma. We recently demonstrated that over expressions of miR-21 and/or miR-155 are frequently occurring in natural killer (NK) cell lymphoma/leukemia and deeply associated with their lymphomagenesis by deregulation of AKT signaling. In this study, we tried to identify tumor suppressor miRNA(s) in malignant lymphomas including B-cell, NK-cell and CD4+T-cell lymphoma, by using quantitative PCR and/or Northern blot analysis. We found that miR-150 in both cell lines and primary samples of NK and T-cell lymphoma showed significantly lower expression than those of normal natural killer cells and CD4+T cells. To examine the role for lymphomagenesis, we stably transduced miR-150 into lymphoma cell lines. Enforced expression of miR-150 in NK/T cell lymphoma cell lines showed increased levels of susceptibility of apoptosis, and showed senescence with reduced levels of telomerase activity and telomere DNA shortening. We further demonstrated that miR-150 directly down regulate AKT2, leading to reduced expression of phosphorylated AKTser473/474 with upregulation of tumor suppressors, Bim, p27 and p53. Since it has been proven that AKT kinase phosphorylate hTERT (human telomerase reverse transcript), downregulation of miR-150 in lymphomas lead to activate telomerase activity, resulting immortalization of the cancer cells. These results suggest that miR-150 play as a role of tumor suppressor in NK/T-cell lymphoma. Our recent and previous report demonstrate that downregulation of miR-150 and upregulation of miR-21/miR-155 collaborately contribute to NK/T-cell lymphomagenesis by deregulating AKT signaling. These findings will give a new insight into the pathogenesis of NK/T cell lymphoma and the miR-150 itself and/or AKT targeting therapy can be a useful against aggressive lymphoma. Disclosures: No relevant conflicts of interest to declare.

Download Full-text