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  • 1
    ISSN: 1569-8041
    Keywords: germinal center ; Hodgkin's disease ; Ig gene rearrangement ; micromanipulation ; Reed–Sternberg cell ; single-cell PCR
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract During their development, B lymphocytes are repeatedly selected for the expression of an appropriate surface receptor: the pre-B-cell receptor at the pre-B-cell stage and surface immunoglobulin (Ig) at the transition from a pre-B cell to a mature B cell. Furthermore, stringent selection for B cells expressing high affinity antibodies operates when antigen-activated B cells proliferate within germinal centers (GC). Here, somatic point mutations are introduced into rearranged V region genes at a high rate, and B cells acquiring favorable mutations are selected to differentiate into memory B cells or plasma cells. In the frame of this developmental scheme, extending a recent analysis, we investigated 10 primary cases of Hodgkin's disease (HD) for B-lineage origin and clonality [1]. Single Hodgkin and Reed–Sternberg (H-RS) cells were micro manipulated from frozen tissue sections and analyzed by PCR for rearranged V genes. Clonal VH and/orV_κ/V_λ gene rearrangements were obtained from 9 of the cases. This shows that H-RS cells represent a clonal, B-lineage-derived population of tumor cells. Somatic mutations were found in all clonal VH gene rearrangements. Interestingly, mutations leading to stop codons in in-frame V gene rearrangements were detected in four cases. Since GC B cells acquiring such crippling mutations are usually efficiently eliminated within the GC, the finding of those mutations indicates that H-RS cells are derived from precursors within the GC that escaped apoptosis by a transforming event.
    Type of Medium: Electronic Resource
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  • 2
    ISSN: 1569-8041
    Keywords: germinal center ; Hodgkin's disease ; Ig gene rearrangement ; micromanipulation ; Reed–Sternberg cell ; single-cell PCR
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract During their development, B lymphocytes are repeatedly selected for theexpression of an appropriate surface receptor: the pre-B-cell receptor atthe pre-B-cell stage and surface immunoglobulin (Ig) at the transition froma pre-B cell to a mature B cell. Furthermore, stringent selection for Bcells expressing high affinity antibodies operates when antigen-activated Bcells proliferate within germinal centers (GC). Here, somatic pointmutations are introduced into rearranged V region genes at a high rate, andB cells acquiring favorable mutations are selected to differentiate intomemory B cells or plasma cells. In the frame of this developmental scheme, extending a recent analysis, weinvestigated 10 primary cases of Hodgkin's disease (HD) for B-lineage originand clonality [1]. Single Hodgkin and Reed–Sternberg (H-RS) cells weremicromanipulated from frozen tissue sections and analyzed by PCR forrearranged V genes. Clonal VH and/orV_κ/V_λ gene rearrangements wereobtained from 9 of the cases. This shows that H-RS cells represent a clonal,B-lineage-derived population of tumor cells. Somatic mutations were found inall clonal VH gene rearrangements. Interestingly, mutationsleading to stop codons in in-frame V gene rearrangements were detected in fourcases. Since GC B cells acquiring such crippling mutations are usuallyefficiently eliminated within the GC, the finding of those mutations indicatesthat H-RS cells are derived from precursors within the GC that escapedapoptosis by a transforming event.
    Type of Medium: Electronic Resource
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  • 3
    ISSN: 1569-8041
    Keywords: cladribine ; 2-CdA ; mantle-cell lymphoma ; treatment
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Purpose: Cladribine (2-chlorodeoxyadenosine, 2-CdA) has been reported to be effective in the treatment of low-grade lymphomas. The objective of this multicenter study was to evaluate the activity of cladribine in mantle-cell lymphomas as first-line therapy or in first relapse using an intermittent two-hour infusion of cladribine. Patients and methods: A total of 47 courses, or an average of four courses per patient, were administered to 12 patients (seven untreated, five relapsed) with 5 mg/m2 cladribine given as an intermittent two-hour infusion over five consecutive days for a maximum of six cycles every four weeks. Results: Cladribine showed activity in patients with mantle-cell lymphomas, achieving a response rate of 58% (95% confidence interval (95% CI): 28%–85%). Myelosuppression was the major toxicity with 17% of grade 3 and 4 neutropenia. Thrombocytopenia was rare with only 2% of grade 3 and 4. Conclusion: These results demonstrate single-agent activity of cladribine in mantle-cell lymphomas using the intermittent two-hour infusion dosage regimen. To further improve treatment results, cladribine should be combined with other agents active in mantle-cell lymphomas.
    Type of Medium: Electronic Resource
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  • 4
    ISSN: 1432-2307
    Keywords: Autoimmunoblastic lymphadenopathy ; T-cell receptor γ ; Immunoglobulin heavy chain ; Clonality ; Polymerase chain reaction
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract The morphological classification of angioimmunoblastic lymphadenopathy (AILD) or T-cell lymphoma of AILD-type (AILD-TCL) is still a subject of considerable difficulty and controversy. The aim of the current study was to examine the value of clinical, morphological, immunohistochemical variables in paraffin-embedded tissues in predicting the clonality of the respective lesion. Fifteen lymph node biopsies derived from 13 patients from Chengdu, China, were diagnosed as AILD or AILD-TCL and included in this study. The specimes were examined using a panel of monoclonal antibodies and a scoring system of morphological features. Clonality of the paraffin-embedded material was investigated using a novel polymerase chain reaction-technique to amplify rearranged T-cell receptor (TCR)-γ sequences. Additional experiments were carried out to investigate the presence of clonal rearrangements of the immunoglobulin heavy chain (IgH) locus. We found clonal rearrangements of the TCR-γ locus in 9 out of 15 lymph node biopsies. In 3 patients, the predominant cell clones carried clonal IgH and TCR-γ rearrangements whereas 1 patient with polyclonal TCR-γ pattern displayed IgH-monoclonality. The statistical evaluation of morphological and immunohistochemical data indicated that no single variable was able significantly to predict the clonality of the lesion. Furthermore, demonstrable clonality for the TCR-γ or the IgH loci of a lesion did not correlate with a bad clinical course. Our data correlate with findings of other studies investigating AILD-TCL in Caucasian populations.
    Type of Medium: Electronic Resource
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  • 5
    ISSN: 1432-2307
    Keywords: Autoimmunoblastic lymphadenopathy ; T-cell receptor γ ; Immunoglobulin heavy chain ; Clonality ; Polymerase chain reaction
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract The morphological classification of angioimmunoblastic lymphadenopathy (AILD) or T-cell lymphoma of AILD-type (AILD-TCL) is still a subject of considerable difficulty and controversy. The aim of the current study was to examine the value of clinical, morphological, immunohistochemical variables in paraffin-embedded tissues in predicting the clonality of the respective lesion. Fifteen lymph node biopsies derived from 13 patients from Chengdu, China, were diagnosed as AILD or AILD-TCL and included in this study. The specimes were examined using a panel of monoclonal antibodies and a scoring system of morphological features. Clonality of the paraffin-embedded material was investigated using a novel polymerase chain reaction-technique to amplify rearranged T-cell receptor (TCR)-γ sequences. Additional experiments were carried out to investigate the presence of clonal rearrangements of the immunoglobulin heavy chain (IgH) locus. We found clonal rearrangements of the TCR-γ locus in 9 out of 15 lymph node biopsies. In 3 patients, the predominant cell clones carried clonal IgH and TCR-γ rearrangements whereas 1 patient with polyclonal TCR-γ pattern displayed IgH-monoclonality. The statistical evaluation of morphological and immunohistochemical data indicated that no single variable was able significantly to predict the clonality of the lesion. Furthermore, demonstrable clonality for the TCR-γ or the IgH loci of a lesion did not correlate with a bad clinical course. Our data correlate with findings of other studies investigating AILD-TCL in Caucasian populations.
    Type of Medium: Electronic Resource
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