Non-invasive B-cell clonality markers may help in the rational approach to HCV SVR cryoglobulinemic patients with persisting manifestations

2018 ◽  
Vol 50 (3) ◽  
pp. e356
Author(s):  
S. Lorini ◽  
L. Gragnani ◽  
V. Santarlasci ◽  
M. Monti ◽  
U. Basile ◽  
...  
Keyword(s):  
B Cell ◽  
Rational Approach ◽  
Non Invasive ◽  
Cell Clonality

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.

The Relevance of VDJ PCR Protocols in Detecting B-Cell Clonal Expansion in Lymphomas and Other Lymphoproliferative Disorders

1995 ◽  
Vol 81 (6) ◽  
pp. 405-409 ◽  
Author(s):  
Valli De Re ◽  
Salvatore De Vita ◽  
Antonino Carbone ◽  
Gianfranco Ferraccioli ◽  
Annunziata Gloghini ◽  
...  
Keyword(s):  
B Cell ◽  
Wide Spectrum ◽  
Clonal Expansion ◽  
Lymphoproliferative Disorders ◽  
Region Gene ◽  
B Cell Malignancy ◽  
Polymerase Chain ◽  
Hodgkin's Lymphomas ◽  
Cell Clonality ◽  
Cell Clonal Expansion

Aims and background The detection of immunoglobulin heavy chain variable (VH)-diversity (DH)-joining (JH) region gene rearrangement by polymerase chain reaction (VDJ PCR) has been recently proposed as a rapid approach to assess B-cell clonality in lymphoproliferative disorders. The aim of the present study was to determine the efficacy of VDJ PCR in a wide spectrum of lymphoproliferative disorders previously characterized by immunohistochemistry and Southern blot (SB). Methods 83 SB-rearranged B-cell non-Hodgkin's lymphomas (NHL) of different histotype, 22 cases of SB-unrearranged classical Hodgkin's disease (HD), 18 cases of HIV-related reactive lymphadenopathy, and 4 frankly pre-lymphomatous lesions (MESA) in the course of Sjögren's syndrome were investigated by 2 different VDJ PCR protocols (FR3, FR2). Results The detection rate in NHL was 64% and 71% using the protocols FR3 and FR2, respectively. However, the overall VDJ PCR efficacy increased to 81% by combining the results of both protocols. In addition, differences in the combined, as well as in the single FR3 or FR2 protocol efficacy, were noted in the different NHL subgroups. B-cell clonality was also detected in 4/22 (18%) SB-unrearranged classical HD cases and in 2/18 (11%) reactive lymphadenopathy cases, whereas it was demonstrated in all the MESA lesions, 2 of them being SB-negative. Conclusions VDJ PCR represents a useful and rapid technique to detect B-cell clonality in NHL, although with some differences depending on the NHL histotype and the panel of primers employed. The technique may also be of value to investigate the possible progression of early B-cell clonal expansion into frankly B-cell malignancy and to contribute to the controversy about the clonal lineage origin of the putative HD malignant cells.

scholarly journals BIOMED-2 PCR assays for IGK gene rearrangements are essential for B-cell clonality analysis in follicular lymphoma

2011 ◽  
Vol 155 (1) ◽  
pp. 84-92 ◽  
Author(s):  
Karen Payne ◽  
Penny Wright ◽  
John W. Grant ◽  
Yuanxue Huang ◽  
Rifat Hamoudi ◽  
...  
Keyword(s):  
Follicular Lymphoma ◽  
B Cell ◽  
Gene Rearrangements ◽  
Clonality Analysis ◽  
Pcr Assays ◽  
Cell Clonality

P073 Analysis of B-cell clonality in composite Hodgkin disease and non-Hodgkin's lymphoma

2007 ◽  
Vol 31 ◽  
pp. S97
Author(s):  
D. Antic ◽  
B. Cikota ◽  
V. Cemerikic ◽  
D. Tomin ◽  
G. Jankovic ◽  
...  
Keyword(s):  
B Cell ◽  
Hodgkin’S Lymphoma ◽  
Hodgkin Disease ◽  
Hodgkin's Lymphoma ◽  
Non Hodgkin’S Lymphoma ◽  
Non Hodgkin's Lymphoma ◽  
Cell Clonality

Granulomatosis linfomatoide cerebral, con clonalidad del receptor de células T. A propósito de un caso.

2020 ◽  
Vol 1 (5) ◽  
Author(s):  
Dr. Raúl Rodríguez ◽  
Dra. Esther Nimchinsky ◽  
Dr. James K Liu ◽  
Dra. Ada Baisre de León
Keyword(s):  
T Cell ◽  
B Cell ◽  
Dna Analysis ◽  
Receptor Gene ◽  
Brain Mri ◽  
B Cell Lymphoma ◽  
Cell Receptor ◽  
Lymphomatoid Granulomatosis ◽  
T Cell Clonality ◽  
Cell Clonality

Lymphomatoid granulomatosis (LG) is a rare, angioinvasive and angiodestructive, EBV-associated B cell lymphoproliferative disorder, which occurs in the setting of immunosuppression. We present the peculiar case of a 67-year-old lady, with systemic lupus erythematous (SLE) and lupus nephritis, on immunosuppressant therapy, who developed a new onset of seizures and was found to have multiple ring enhancing lesions on brain MRI. A biopsy of one of the lesions revealed lymphomatoid granulomatosis, grade I. DNA analysis of the neoplasm, showed T-cell receptor gene rearrangement (TRG) and no evidence of B-cell rearrangement, which is an unusual finding. On further examination several lung nodules were identified on a CT scan of the chest, a characteristic of LG. Key words: Cerebral lymphomatoid granulomatosis, T cell clonality, Epstein Bar virus, Immunodeficiency associated B-cell lymphoma

High Prevalence of B-Cell Clonality in Patients with Gaucher’s Disease.

Blood ◽  
2004 ◽  
Vol 104 (11) ◽  
pp. 2391-2391 ◽  
Author(s):  
Derralynn A. Hughes ◽  
Veronique M. Duke ◽  
Robert J. Baker ◽  
Faith Wright ◽  
Letizia Foroni ◽  
...  
Keyword(s):  
B Cell ◽  
Gaucher Disease ◽  
Haematological Malignancy ◽  
Chain Gene ◽  
Heavy Chain Gene ◽  
Immunoglobulin Heavy Chain Gene ◽  
Bulk Storage ◽  
Clonal Population ◽  
Polyclonal Gammopathy ◽  
Cell Clonality

Abstract Haematological malignancy occurs in patients with Gaucher Disease at an incidence 15 fold greater than in the non-Gaucher population. Little is understood regarding the role of glucosyl ceramide acculmulation in immune system pathology or in the development of cancer in Gaucher Disease. Furthermore whilst enzyme replacement therapy (ERT) with recombinant glucocerebrosidase has been successful in reversing symptoms relating to bulk storage e.g. hepatosplenomegaly and bone marrow infiltration, its effects on the pathogenesis of malignancy are unknown. We have measured the levels of immunlglobulin in 63 patients with Gaucher disease receiving ERT for up to 10 years and have investigated the incidence of clonal B cell populations by flow cytometry, immunoglobulin heavy chain gene rearrangement analysis, and measurement of paraproteins by electropheresis and immunofixation. Evidence of high level of immune stimulation was found by morphological and immunoglobin analysis. Examination of peripheral blood revealed atypical lymphocyte morphology in 53% Gaucher patients whilst 50.7% patients were found to have levels of immunoglobulins significantly higher than those found in healthy adults. There were no sex or age related differences between those patients with elevated immunoglobulins (18 male; median age 40yrs, 14 female; median age 48 years) and those with normal levels (13 male median age 41 years, 18 female; median age 47.5 years). Elevation of one, two or three immunoglobulin subclasses was detected in 36%, 13.1% and 1.6% of patients respectively. In patients with IgM polyclonal gammopathy levels of immunoglobulin normalised with ERT. This was not the case with IgG and IgA gammopathies which were unaffected by ERT even after 10 years of treatment. No patient with normal immunoglobulin levels prior to treatment developed a gammopathy after initiation of ERT Evidence of B-cell clonality was found in 23% of patients. 13.4% had measurable paraproteins, 9.3% exhibited a IgM+, IgD+, FMC7+ monoclonal population by flow cytometry and 26.9% had clonal immunoglobulin heavy chain gene rearrangements of which 43% were in frame and therefore functional. There was no relationship between genotype, absolute lymphocyte count (median 1.5 x109 in all groups) and age (median 45.5 years with clonal population and 44 years without) or duration of ERT (median 5.25 years with clonal population and 6.5 years without) and the existence of clonality. Our data confirms the existence of high levels of immune stimulation and B cell clonality in patients with Gaucher disease. In contrast to features of bulk storage of glucosyl ceramide, the polyclonal gammopathy and B cell clonality is not reversed by ERT and may therefore occur at low levels of storage. The existence of multiple markers of clonality will allow the response of individual patients to different modalities of therapy to be followed, and the pathophysiology of haematological malignancy to be further assessed.

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