scholarly journals T-Cell Lymphoma Clonality by Copy Number Variation Analysis of T-Cell Receptor Genes

Cancers ◽  
2021 ◽  
Vol 13 (2) ◽  
pp. 340
Author(s):  
Ming Liang Oon ◽  
Jing Quan Lim ◽  
Bernett Lee ◽  
Sai Mun Leong ◽  
Gwyneth Shook-Ting Soon ◽  
...  
Keyword(s):  
T Cell ◽  
B Cell ◽  
T Cell Receptor ◽  
Copy Number ◽  
Nk Cell ◽  
Cell Receptor ◽  
T Cell Lymphomas ◽  
Number Variation ◽  
Diagnostic Applications ◽  
Cell Clonality

T-cell lymphomas arise from a single neoplastic clone and exhibit identical patterns of deletions in T-cell receptor (TCR) genes. Whole genome sequencing (WGS) data represent a treasure trove of information for the development of novel clinical applications. However, the use of WGS to identify clonal T-cell proliferations has not been systematically studied. In this study, based on WGS data, we identified monoclonal rearrangements (MRs) of T-cell receptors (TCR) genes using a novel segmentation algorithm and copy number computation. We evaluated the feasibility of this technique as a marker of T-cell clonality using T-cell lymphomas (TCL, n = 44) and extranodal NK/T-cell lymphomas (ENKTLs, n = 20), and identified 98% of TCLs with one or more TCR gene MRs, against 91% detected using PCR. TCR MRs were absent in all ENKTLs and NK cell lines. Sensitivity-wise, this platform is sufficiently competent, with MRs detected in the majority of samples with tumor content under 25% and it can also distinguish monoallelic from biallelic MRs. Understanding the copy number landscape of TCR using WGS data may engender new diagnostic applications in hematolymphoid pathology, which can be readily adapted to the analysis of B-cell receptor loci for B-cell clonality determination.

Copy number variation and association over T-cell receptor genes—influence of DNA source

2010 ◽  
Vol 62 (8) ◽  
pp. 561-567 ◽  
Author(s):  
Christine Schwienbacher ◽  
Alessandro De Grandi ◽  
Christian Fuchsberger ◽  
Maurizio F. Facheris ◽  
Mirija Svaldi ◽  
...  
Keyword(s):  
T Cell ◽  
Copy Number Variation ◽  
T Cell Receptor ◽  
Copy Number ◽  
Cell Receptor ◽  
T Cell Receptor Genes ◽  
Number Variation

scholarly journals CD5-CD56+ T-cell receptor silent peripheral T-cell lymphomas are natural killer cell lymphomas [see comments]

Blood ◽  
1996 ◽  
Vol 87 (4) ◽  
pp. 1466-1473 ◽  
Author(s):  
JF Emile ◽  
ML Boulland ◽  
C Haioun ◽  
P Kanavaros ◽  
T Petrella ◽  
...  
Keyword(s):  
T Cell ◽  
Nk Cells ◽  
Natural Killer ◽  
T Cell Receptor ◽  
Nk Cell ◽  
Cell Receptor ◽  
Cell Markers ◽  
Clonal Rearrangement ◽  
T Cell Lymphomas ◽  
Peripheral T Cell Lymphomas

Non-Hodgkin's lymphomas are divided into B- and T-cell neoplasms. The existence and the clinical relevance of lymphomas derived from the third lymphocyte lineage, ie, natural killer (NK) cells are still controversial. NK cells are lymphocytes that mediate cytotoxicity without prior sensitization. NK cells also have phenotypic and genotypic characteristics: they express the NK-related antigen CD56, T- cell markers such as CD2 and CD7, but do not express CD5 and T-cell receptor (TCR) proteins, and their TCR locus is not rearranged. Therefore, if NK cell lymphomas exist, they should express some T-cell markers, but not alpha beta or gamma delta TCR proteins. Such lymphomas are actually called TCR silent peripheral T cell lymphomas (PTCL). To detect and characterize NK cell lymphomas, we investigated the immunophenotype and immunogenotype of 35 patients with TCR silent PTCL. The first group included 16 patients with a lymphoma of CD5-CD56+ phenotype, which is identical to normal NK cells. These patients had either a nasal/nasopharyngeal lymphoma (11 cases) or a lymphoma with predominant non-nasal/non-nodal initial involvement (five cases). Eight of the nine cases for which immunogenotypic data were available lacked clonal rearrangement of the TCR gamma genes. Thus, these tumors are likely to be NK cell lymphomas. The second group of 15 cases had a CD5+ phenotype (14 were CD56-, and 1 was CD56+) and clonal rearrangement of TCR gamma genes, indicating that they were true PTCL with unproductive TCR rearrangement. The four remaining cases were CD5- CD56- lymphomas and disclosed either a clonal (two cases) or no clonal (two cases) rearrangements of the TCR gamma genes. Altogether these findings show that CD5-CD56+ so-called “TCR silent PTCL” bear the immunophenotype and immunogenotype of normal NK cells and display peculiar clinical features distinct from true PTCL.

scholarly journals Case of a CD3 Negative Hepatosplenic T-Cell Lymphoma: Diagnostic and Therapeutic Challenges

2019 ◽  
Vol 2019 ◽  
pp. 1-4
Author(s):  
Laura Alder ◽  
Scott Graupner ◽  
Guanhua Lai ◽  
Victor Yazbeck
Keyword(s):  
T Cell ◽  
T Cell Receptor ◽  
Nk Cell ◽  
Cell Lymphoma ◽  
Single Agent ◽  
Cell Receptor ◽  
T Cell Lymphoma ◽  
Receptor Expression ◽  
T Cell Lymphomas ◽  
Hepatosplenic T Cell Lymphoma

Hepatosplenic T-cell lymphomas (TCLs) are a rare, aggressive subset of TCLs, accounting for less than 5% of all peripheral T-cell and natural killer (NK) cell lymphomas. We report the case of a CD3 negative hepatosplenic T-cell lymphoma in a 42-year-old female, who presented with left-sided abdominal pain. She underwent a liver biopsy that showed marked abnormal sinusoidal lymphoid infiltration. PET scan revealed increased splenic and pharyngeal lymph node uptake. Immunophenotype was remarkable for negative CD3, gamma delta T-cell receptor, and alpha beta-T-cell receptor expression. She received 6 cycles of DA-EPOCH, had primary refractory disease and then underwent palliative splenectomy secondary to painful necrosis. Then, she was started on pralatrexate as a single agent and then in combination with romidepsin as a potential bridge to an allogeneic stem cell transplantation from her sibling.

scholarly journals Large-scale proteomic analysis of tyrosine-phosphorylation induced by T-cell receptor or B-cell receptor activation reveals new signaling pathways

PROTEOMICS ◽  
2009 ◽  
Vol 9 (13) ◽  
pp. 3549-3563 ◽  
Author(s):  
Masaki Matsumoto ◽  
Koji Oyamada ◽  
Hidehisa Takahashi ◽  
Takamichi Sato ◽  
Shigetsugu Hatakeyama ◽  
...  
Keyword(s):  
T Cell ◽  
B Cell ◽  
Signaling Pathways ◽  
Tyrosine Phosphorylation ◽  
T Cell Receptor ◽  
Proteomic Analysis ◽  
Large Scale ◽  
Cell Receptor ◽  
Receptor Activation ◽  
B Cell Receptor

Ig alpha and Ig beta are functionally homologous to the signaling proteins of the T-cell receptor

1994 ◽  
Vol 14 (2) ◽  
pp. 1095-1103
Author(s):  
A L Burkhardt ◽  
T Costa ◽  
Z Misulovin ◽  
B Stealy ◽  
J B Bolen ◽  
...  
Keyword(s):  
Signal Transduction ◽  
T Cells ◽  
T Cell ◽  
B Cell ◽  
T Cell Receptor ◽  
Interleukin 2 ◽  
Antigen Receptor ◽  
Cell Receptor ◽  
Antigen Receptors ◽  
Cell Antigen

Signal transduction by antigen receptors and some Fc receptors requires the activation of a family of receptor-associated transmembrane accessory proteins. One common feature of the cytoplasmic domains of these accessory molecules is the presence is at least two YXXA repeats that are potential sites for interaction with Src homology 2 domain-containing proteins. However, the degree of similarity between the different receptor-associated proteins varies from that of T-cell receptor (TCR) zeta and Fc receptor RIIIA gamma chains, which are homologous, to the distantly related Ig alpha and Ig beta proteins of the B-cell antigen receptor. To determine whether T- and B-cell antigen receptors are in fact functionally homologous, we have studied signal transduction by chimeric immunoglobulins bearing the Ig alpha or Ig beta cytoplasmic domain. We found that Ig alpha and Ig beta cytoplasmic domains were able to activate Ca2+ flux, interleukin-2 secretion, and phosphorylation of the same group of cellular substrates as the TCR in transfected T cells. Chimeric proteins were then used to examine the minimal requirements for activation of the Fyn, Lck, and ZAP kinases in T cells. Both Ig alpha and Ig beta were able to trigger Fyn, Lck, and ZAP directly without involvement of TCR components. Cytoplasmic tyrosine residues in Ig beta were required for recruitment and activation of ZAP-70, but these amino acids were not essential for the activation of Fyn and Lck. We conclude that Fyn and Lck are able to recognize a clustered nonphosphorylated immune recognition receptor, but activation of these kinases is not sufficient to induce cellular responses such as Ca2+ flux and interleukin-2 secretion. In addition, the molecular structures involved in antigen receptor signaling pathways are conserved between T and B cells.

Natural Killer–Cell Lymphoma Involving the Gynecologic Tract

2000 ◽  
Vol 124 (10) ◽  
pp. 1510-1513 ◽  
Author(s):  
Paulette Mhawech ◽  
L. Jeffrey Medeiros ◽  
Carlos Bueso-Ramos ◽  
Donna M. Coffey ◽  
Alfredo F. Gei ◽  
...  
Keyword(s):  
T Cell ◽  
Natural Killer ◽  
T Cell Receptor ◽  
Nk Cell ◽  
Cell Lymphoma ◽  
Killer Cell ◽  
Cell Receptor ◽  
Lymphoid Cells ◽  
Gene Rearrangements ◽  
Neoplastic Cells

Abstract Non-Hodgkin lymphomas (NHL) can involve the gynecologic tract, most often as a manifestation of systemic involvement, and most cases reported have been of B-cell lineage. We describe 2 women with natural killer (NK)-cell lymphoma involving the gynecologic tract that initially presented with vaginal bleeding. In case 1, the patient had a stage IE nasal-type NK-cell lymphoma involving the cervix. The tumor was composed of medium-sized, irregular lymphoid cells with angioinvasion and necrosis. In case 2, the patient had a stage IV blastoid NK-cell lymphoma/leukemia infiltrating all organs in a hysterectomy and bilateral salpingo-oophorectomy specimen. Subsequent biopsy specimens revealed that the bone marrow and lymph nodes were also involved. The neoplasm was composed of small to medium lymphoid cells with fine nuclear chromatin. Case 1 was assessed immunohistochemically and the neoplastic cells were positive for CD3, CD56, and TIA-1. Case 2 was analyzed using both immunohistochemical and flow cytometry methods. The neoplastic cells were positive for cytoplasmic CD3, CD4, CD7, CD43, CD45, and CD56 and were negative for surface CD3. Both cases were negative for Epstein-Barr virus (EBV) ribonucleic acid (RNA) and molecular studies showed no evidence of T-cell receptor γ chain gene rearrangements. The immunophenotype and absence of T-cell receptor gene rearrangements support NK-cell origin. We report these cases to illustrate that NK-cell lymphomas can involve, and rarely arise in, the gynecologic tract.

Prognostic value of T-cell receptor γ rearrangement in peripheral blood or bone marrow of patients with peripheral T-cell lymphomas

2008 ◽  
Vol 49 (2) ◽  
pp. 237-246 ◽  
Author(s):  
Christian SchüTzinger ◽  
Harald Esterbauer ◽  
Gregor Hron ◽  
Cathrin Skrabs ◽  
Martin Uffmann ◽  
...  
Keyword(s):  
Bone Marrow ◽  
T Cell ◽  
T Cell Receptor ◽  
Peripheral Blood ◽  
Prognostic Value ◽  
Cell Receptor ◽  
T Cell Lymphomas ◽  
Peripheral T Cell Lymphomas
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