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  • 1
    Electronic Resource
    Electronic Resource
    Normal and malignant B-cell development with special reference to Hodgkin's disease (1997)
    Springer
    Annals of oncology 8 (1997), S. 79-81 
    Details
    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
    URL: http://dx.doi.org/10.1023/A:1008294602841
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  • 2
    Electronic Resource
    Electronic Resource
    Normal and malignant B-cell development with special reference to Hodgkin's disease (1997)
    Springer
    Annals of oncology 8 (1997), S. 79-81 
    Details
    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
    URL: http://dx.doi.org/10.1023/A:1008294602841
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    Paper (German National Licenses)
    Fulltext
  • 3
    Electronic Resource
    Electronic Resource
    Treatment of mantle-cell lymphomas with intermittent two-hour infusion of cladribine as first-line therapy or in first relapse (1999)
    Springer
    Annals of oncology 10 (1999), S. 115-117 
    Details
    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
    URL: http://dx.doi.org/10.1023/A:1008325212484
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    Paper (German National Licenses)
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  • 4
    Electronic Resource
    Electronic Resource
    Hodgkin-Zellen sind klonale B-Zellen auf unterschiedlichen Stufen der Entwicklung (1995)
    Springer
    Der Pathologe 16 (1995), S. 88-93 
    Details
    ISSN: 1432-1963
    Keywords: Schlüsselwörter Hodgkin-Zellen ; Klonalität ; Einzelzell-PCR ; B-Zelldifferenzierung ; Key words Hodgkin cells ; Clonality ; Single cell PCR ; B-cell differentiation
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Description / Table of Contents: Summary Hodgkin's disease, especially its biology and pathogenesis, has been under discussion for more than 160 years. Numerous investigations have focused on the nature and clonality of Hodgkin cells, but so far no definitive answer have been yielded by immunohistochemistry, Southen blotting and PCR. However, the use of single-cell PCR has now made it possible to answer the question of the derivation of Hodgkin cells. Using a micromanipulator, Hodgkin cells can be picked out of histological sections and B-cell specific gene rearrangements (VDJ) can be amplified. With this technique it has proved possible to demonstrate the B-cell derivation of Hodgkin cells and their clonality. Mutated immunoglobulin genes in lymphocyte-predominant Hodgkin's disease indicate a germinal center cell origin of Hodgkin cells of this type. These findings, however, do not exclude cases of Hodgkin's disease with Hodgkin cells with a T-cell genotype.
    Notes: Zusammenfassung Der Morbus Hodgkin ist auch heute, mehr als 160 Jahre nach seiner Erstbeschreibung durch Thomas Hodgkin, insbesondere hinsichtlich Biologie und Pathogenese, Gegenstand vieler kontroverser Diskussionen. Im Vordergrund zahlreicher Untersuchungen stand die Frage nach der Natur der Hodgkin-Zellen sowie ihrer Klonalität. Diese Fragestellungen ließen sich bislang mit den zur Verfügung stehenden Techniken, wie Immunhistochemie, Southern blotting und Polymerasekettenreaktion (PCR) nicht schlüssig beantworten. Erst der Einsatz von Einzelzell-PCR-Verfahren erlaubt es, die Natur der Hodgkin-Zelle aufzuklären. Mit Hilfe eines Mikromanipulators können einzelne Hodgkin-Zellen aus Gewebsschnitten entfernt und für B-Zellen spezifische Genumlagerungen (VDJ) amplifiziert werden. Durch diese Technik läßt sich die B-Zellherkunft von Hodgkin-Zellen und deren Klonalität nachweisen. Mutierte Immunglobulingene in Hodgkin-Zellen des lymphozytenreichen Typs sind Hinweis auf deren Keimzentrumszellgenese. Die bislang gewonnenen Daten schließen jedoch nicht aus, daß auch Morbus Hodgkin-Fälle existieren, deren Tumorzellen von T-Lymphozyten abstammen.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/s002920050081
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    Paper (German National Licenses)
    Fulltext
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