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Juergen Wolf - One of the best experts on this subject based on the ideXlab platform.
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Loss of heterozygosity in the Hodgkin-Reed Sternberg Cell line L1236
British Journal of Cancer, 2001Co-Authors: Andrea Staratschek-jox, Volker Diehl, M. Kornacker, R Kurt Thomas, Thomas Zander, Nadia Massoudi, Jörn Bullerdiek, Christa Fonatsch, Juergen WolfAbstract:Hodgkin-Reed Sternberg Cells are derived from germinal centre B-Cells in most cases. Somatic mutations affecting their rearranged immunoglobulin genes were detected, rendering potential functional rearrangements non-functional. Under physiological conditions such Cells would be designated to undergo apoptosis within the germinal centre. In search for the specific transforming event that prevents Hodgkin-Reed Sternberg Cells from programmed Cell death, cytogenetic analyses were broadly performed but did not reveal specific chromosomal aberrations. Analysis of these Cells on the molecular level is difficult to perform due to the scarcity of the Cells in the lymphoma tissue and the given limitations of in situ studies. To overcome these limitations, the Cell line L1236, known to be derived from Hodgkin-Reed Sternberg Cells in situ, was chosen for allelotype analysis. Using a panel of microsatellite loci assigned to nearly all chromosomal arms, regions of loss of heterozygosity were detected on chromosomal arms 6p, 9q and 17p. The size of lost segments was estimated by amplification of additional microsatellite loci mapped to the respective regions. Further analyses of single Hodgkin-Reed Sternberg Cells will reveal whether LOH affecting these regions is a recurrent event in HD and to which extent the smallest commonly affected region can be estimated.
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detection of a hodgkin Reed Sternberg Cell specific immunoglobulin gene rearrangement in the serum dna of a patient with hodgkin s disease
British Journal of Haematology, 1999Co-Authors: M. Kornacker, Volker Diehl, Andrea Jox, Martina Vockerodt, Hans Tesch, Heribert Bohlen, Juergen WolfAbstract:We analysed multiple serum samples from a patient with mixed Cellularity Hodgkin's disease for the Hodgkin/Reed-Sternberg Cell clone-specific rearranged Ig gene sequence. The clone-specific sequence could be detected in DNA extracted from a serum sample obtained during clinical relapse but not in serum samples obtained during or after treatment following relapse.
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Detection of a Hodgkin/Reed-Sternberg Cell specific immunoglobulin gene rearrangement in the serum DNA of a patient with Hodgkin's disease
British Journal of Haematology, 1999Co-Authors: M. Kornacker, Volker Diehl, Andrea Jox, Martina Vockerodt, Hans Tesch, Heribert Bohlen, Juergen WolfAbstract:We analysed multiple serum samples from a patient with mixed Cellularity Hodgkin's disease for the Hodgkin/Reed-Sternberg Cell clone-specific rearranged Ig gene sequence. The clone-specific sequence could be detected in DNA extracted from a serum sample obtained during clinical relapse but not in serum samples obtained during or after treatment following relapse.
Fabienne Meggetto - One of the best experts on this subject based on the ideXlab platform.
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Comparative analysis of oncogenic properties and nuclear factor-kappaB activity of latent membrane protein 1 natural variants from Hodgkin's lymphoma's Reed-Sternberg Cells and normal B-lymphocytes.
Haematologica, 2009Co-Authors: Nathalie Faumont, Aurélie Chanut, Alan Benard, Nadine Cogné, Georges Delsol, Jean Feuillard, Fabienne MeggettoAbstract:BACKGROUND: In Epstein-Barr virus-associated Hodgkin's lymphomas, neoplastic Reed-Sternberg Cells and surrounding non-tumor B-Cells contain different variants of the LMP1-BNLF1 oncogene. In this study, we raised the question of functional properties of latent membrane protein 1 (LMP1) natural variants from both Reed-Sternberg and non-tumor B-Cells. DESIGN AND METHODS: Twelve LMP1 natural variants from Reed-Sternberg Cells, non-tumor B-Cells of Hodgkin's lymphomas and from B-Cells of benign reactive lymph nodes were cloned, sequenced and stably transfected in murine recombinant interleukin-3-dependent Ba/F3 Cells to search for relationships between LMP1 Cellular origin and oncogenic properties as well as nuclear factor-kappaB activation, and apoptosis protection. RESULTS: LMP1 variants of Reed-Sternberg Cell origin were often associated with increased mutation rate and with recurrent genetic events, such as del15bp associated with S to N replacement at codon 309, and four substitutions I85L, F106Y, I122L, and M129I. Oncogenic potential (growth factor-independence plus clonogenicity) was consistently associated with LMP1 variants from Reed-Sternberg Cells, but inconstantly for LMP1-variants from non-tumor B-Cells. Analysis of LMP1 variants from both normal B-Cells and Reed-Sternberg Cells indicates that protection against apoptosis through activation of nuclear factor-kappaB - whatever the Cellular origin of LMP1 - was maintained intact, regardless of the mutational pattern. CONCLUSIONS: Taken together, our results demonstrate that preserved nuclear factor-kappaB activity and protection against apoptosis would be the minimal prerequisites for all LMP1 natural variants from both normal and tumor Cells in Hodgkin's lymphomas, and that oncogenic potential would constitute an additional feature for LMP1 natural variants in Reed-Sternberg Cells.
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Comparative analysis of oncogenic properties and nuclear factor-κB activity of latent membrane protein 1 natural variants from Hodgkin’s lymphoma’s Reed-Sternberg Cells and normal B-lymphocytes
Haematologica, 2009Co-Authors: Nathalie Faumont, Aurélie Chanut, Alan Benard, Nadine Cogné, Georges Delsol, Jean Feuillard, Fabienne MeggettoAbstract:Background In Epstein-Barr virus-associated Hodgkin’s lymphomas, neoplastic Reed-Sternberg Cells and surrounding non-tumor B-Cells contain different variants of the LMP1-BNLF1 oncogene. In this study, we raised the question of functional properties of latent membrane protein 1 (LMP1) natural variants from both Reed-Sternberg and non-tumor B-Cells. Design and Methods Twelve LMP1 natural variants from Reed-Sternberg Cells, non-tumor B-Cells of Hodgkin’s lymphomas and from B-Cells of benign reactive lymph nodes were cloned, sequenced and stably transfected in murine recombinant interleukin-3-dependent Ba/F3 Cells to search for relationships between LMP1 Cellular origin and oncogenic properties as well as nuclear factor-κB activation, and apoptosis protection. Results LMP1 variants of Reed-Sternberg Cell origin were often associated with increased mutation rate and with recurrent genetic events, such as del15bp associated with S to N replacement at codon 309, and four substitutions I85L, F106Y, I122L, and M129I. Oncogenic potential (growth factor-independence plus clonogenicity) was consistently associated with LMP1 variants from Reed-Sternberg Cells, but inconstantly for LMP1-variants from non-tumor B-Cells. Analysis of LMP1 variants from both normal B-Cells and Reed-Sternberg Cells indicates that protection against apoptosis through activation of nuclear factor-κB - whatever the Cellular origin of LMP1 - was maintained intact, regardless of the mutational pattern. Conclusions Taken together, our results demonstrate that preserved nuclear factor-κB activity and protection against apoptosis would be the minimal prerequisites for all LMP1 natural variants from both normal and tumor Cells in Hodgkin’s lymphomas, and that oncogenic potential would constitute an additional feature for LMP1 natural variants in Reed-Sternberg Cells.
M. Kornacker - One of the best experts on this subject based on the ideXlab platform.
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Loss of heterozygosity in the Hodgkin-Reed Sternberg Cell line L1236
British Journal of Cancer, 2001Co-Authors: Andrea Staratschek-jox, Volker Diehl, M. Kornacker, R Kurt Thomas, Thomas Zander, Nadia Massoudi, Jörn Bullerdiek, Christa Fonatsch, Juergen WolfAbstract:Hodgkin-Reed Sternberg Cells are derived from germinal centre B-Cells in most cases. Somatic mutations affecting their rearranged immunoglobulin genes were detected, rendering potential functional rearrangements non-functional. Under physiological conditions such Cells would be designated to undergo apoptosis within the germinal centre. In search for the specific transforming event that prevents Hodgkin-Reed Sternberg Cells from programmed Cell death, cytogenetic analyses were broadly performed but did not reveal specific chromosomal aberrations. Analysis of these Cells on the molecular level is difficult to perform due to the scarcity of the Cells in the lymphoma tissue and the given limitations of in situ studies. To overcome these limitations, the Cell line L1236, known to be derived from Hodgkin-Reed Sternberg Cells in situ, was chosen for allelotype analysis. Using a panel of microsatellite loci assigned to nearly all chromosomal arms, regions of loss of heterozygosity were detected on chromosomal arms 6p, 9q and 17p. The size of lost segments was estimated by amplification of additional microsatellite loci mapped to the respective regions. Further analyses of single Hodgkin-Reed Sternberg Cells will reveal whether LOH affecting these regions is a recurrent event in HD and to which extent the smallest commonly affected region can be estimated.
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detection of a hodgkin Reed Sternberg Cell specific immunoglobulin gene rearrangement in the serum dna of a patient with hodgkin s disease
British Journal of Haematology, 1999Co-Authors: M. Kornacker, Volker Diehl, Andrea Jox, Martina Vockerodt, Hans Tesch, Heribert Bohlen, Juergen WolfAbstract:We analysed multiple serum samples from a patient with mixed Cellularity Hodgkin's disease for the Hodgkin/Reed-Sternberg Cell clone-specific rearranged Ig gene sequence. The clone-specific sequence could be detected in DNA extracted from a serum sample obtained during clinical relapse but not in serum samples obtained during or after treatment following relapse.
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Detection of a Hodgkin/Reed-Sternberg Cell specific immunoglobulin gene rearrangement in the serum DNA of a patient with Hodgkin's disease
British Journal of Haematology, 1999Co-Authors: M. Kornacker, Volker Diehl, Andrea Jox, Martina Vockerodt, Hans Tesch, Heribert Bohlen, Juergen WolfAbstract:We analysed multiple serum samples from a patient with mixed Cellularity Hodgkin's disease for the Hodgkin/Reed-Sternberg Cell clone-specific rearranged Ig gene sequence. The clone-specific sequence could be detected in DNA extracted from a serum sample obtained during clinical relapse but not in serum samples obtained during or after treatment following relapse.
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detection of identical hodgkin Reed Sternberg Cell specific immunoglobulin gene rearrangements in a patient with hodgkin s disease of mixed Cellularity subtype at primary diagnosis and in relapse two and a half years later
Annals of Oncology, 1998Co-Authors: Andrea Jox, Volker Diehl, M. Kornacker, Thomas Zander, Ralf Kuppers, Holger Kanzler, J WolfAbstract:Summary Background The malignant nature of Hodgkin–Reed Sternberg (H–RS) Cells has been questioned due to their scarcity in lymphoma tissues. Recently, using micromanipulation of H–RS Cells and single Cell PCR evidence was obtained that H–RS Cells represent a clonal B-Cell population. In these studies H–RS Cells were isolated from each one lymph node for a given case. In classical Hodgkin’s disease (HD) it thus could not be ruled out that H–RS Cell clonality reflected a locally restricted clonal proliferation. We analysed biopsy specimens from a patient suffering from HD for the presence of clonally related H–RS Cells at primary diagnosis and during relapse of the disease. Materials and methods In 1994 the H–RS Cell line L1236 was generated from the peripheral blood of a patient suffering from a disseminating relapse of HD of mixed Cellularity subtype. The patient had relapsed despite intensive treatment including high dose chemotherapy and autologous bone marrow transplantation. The clonal identity of this Cell line with H–RS Cells in situ was proven by amplifying identical Ig gene rearrangements of the Cell line as well as of single H–RS Cells picked from the patients bone marrow. Primers covering the CDR3 region were chosen from the H-RS Cell specific VH1 gene rearrangement to detect H–RS Cells of the identical clone by amplifying the rearranged VH1 genes in tissue samples obtained during disseminating relapsing disease and at primary diagnosis of HD in 1991. Results The H–RS Cell specific DNA sequence was detected in all affected tissues analysed including the cervical lymph node which has been exstirpated at primary diagnosis. Conclusion This finding indicates the existence of a clonal H–RS Cell population during the first manifestation of HD and persistence and dissemination of this clone despite aggressive treatment. Thus, in the described case the malignant nature of H–RS Cells defined by dissemination and recurrence of the identical H–RS Cell clone in relapsing disease is proven.
Volker Diehl - One of the best experts on this subject based on the ideXlab platform.
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deregulation of immunoglobulin gene transcription in the hodgkin Reed Sternberg Cell line l1236
British Journal of Haematology, 2001Co-Authors: Andrea Staratschekjox, Volker Diehl, Udo Holtick, Jurgen WolfAbstract:Hodgkin-Reed Sternberg (H-RS) Cells harbour clonal immunoglobulin gene (Ig) rearrangements in almost all cases of classical Hodgkin's disease but lack Ig gene expression. In the H-RS Cell line L1236, a somatic mutation of the Ig heavy-chain gene promoter octamer motif has been described as a putative reason for absence of Ig gene expression. We addressed transcriptional activity of this mutated promoter by performing reporter gene studies and gel retardation assays. The results showed that the mutation outside the coding region of the rearranged Ig gene in L1236 Cells leads to downregulation of Ig gene expression in H-RS Cells.
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Cell fusion is not involved in the generation of giant Cells in the hodgkin Reed Sternberg Cell line l1236
American Journal of Hematology, 2001Co-Authors: Elena Benenson, Volker Diehl, Marc Beyer, Oliver Gresch, Andreas Draube, Jurgen WolfAbstract:The mechanism of multinucleated Cell formation in Hodgkin's disease has not yet been elucidated. We asked whether the giant multinucleated Cells of the H-RS Cell line L1236 develop via fusion of the predominant smaller Cells. As a positive control for the fusion assay, human B Cells from the B-Cell lymphoma Cell line BJA-B were split into two fractions, stained with the fluorochromes CMTMR and CMFDA, respectively, and fused using the polyethylene glycol 1500 Cell hybridization protocol. Double-stained Cells indicating fusion of BJA-B Cells were detectable for up to 5 days. In parallel, L1236 Cells were split into two fractions, stained with the fluorochromes, and mixed. No double-stained L1236 Cells were detected. The same result was obtained when using FACS-sorted small mononuclear L1236 Cells. It is thus concluded that the large multinucleated Cells of the monoclonal H-RS Cell line L1236 have emerged by endomitosis rather than by spontaneous Cell fusion.
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Loss of heterozygosity in the Hodgkin-Reed Sternberg Cell line L1236
British Journal of Cancer, 2001Co-Authors: Andrea Staratschek-jox, Volker Diehl, M. Kornacker, R Kurt Thomas, Thomas Zander, Nadia Massoudi, Jörn Bullerdiek, Christa Fonatsch, Juergen WolfAbstract:Hodgkin-Reed Sternberg Cells are derived from germinal centre B-Cells in most cases. Somatic mutations affecting their rearranged immunoglobulin genes were detected, rendering potential functional rearrangements non-functional. Under physiological conditions such Cells would be designated to undergo apoptosis within the germinal centre. In search for the specific transforming event that prevents Hodgkin-Reed Sternberg Cells from programmed Cell death, cytogenetic analyses were broadly performed but did not reveal specific chromosomal aberrations. Analysis of these Cells on the molecular level is difficult to perform due to the scarcity of the Cells in the lymphoma tissue and the given limitations of in situ studies. To overcome these limitations, the Cell line L1236, known to be derived from Hodgkin-Reed Sternberg Cells in situ, was chosen for allelotype analysis. Using a panel of microsatellite loci assigned to nearly all chromosomal arms, regions of loss of heterozygosity were detected on chromosomal arms 6p, 9q and 17p. The size of lost segments was estimated by amplification of additional microsatellite loci mapped to the respective regions. Further analyses of single Hodgkin-Reed Sternberg Cells will reveal whether LOH affecting these regions is a recurrent event in HD and to which extent the smallest commonly affected region can be estimated.
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detection of a hodgkin Reed Sternberg Cell specific immunoglobulin gene rearrangement in the serum dna of a patient with hodgkin s disease
British Journal of Haematology, 1999Co-Authors: M. Kornacker, Volker Diehl, Andrea Jox, Martina Vockerodt, Hans Tesch, Heribert Bohlen, Juergen WolfAbstract:We analysed multiple serum samples from a patient with mixed Cellularity Hodgkin's disease for the Hodgkin/Reed-Sternberg Cell clone-specific rearranged Ig gene sequence. The clone-specific sequence could be detected in DNA extracted from a serum sample obtained during clinical relapse but not in serum samples obtained during or after treatment following relapse.
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Detection of a Hodgkin/Reed-Sternberg Cell specific immunoglobulin gene rearrangement in the serum DNA of a patient with Hodgkin's disease
British Journal of Haematology, 1999Co-Authors: M. Kornacker, Volker Diehl, Andrea Jox, Martina Vockerodt, Hans Tesch, Heribert Bohlen, Juergen WolfAbstract:We analysed multiple serum samples from a patient with mixed Cellularity Hodgkin's disease for the Hodgkin/Reed-Sternberg Cell clone-specific rearranged Ig gene sequence. The clone-specific sequence could be detected in DNA extracted from a serum sample obtained during clinical relapse but not in serum samples obtained during or after treatment following relapse.
Nathalie Faumont - One of the best experts on this subject based on the ideXlab platform.
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Comparative analysis of oncogenic properties and nuclear factor-kappaB activity of latent membrane protein 1 natural variants from Hodgkin's lymphoma's Reed-Sternberg Cells and normal B-lymphocytes.
Haematologica, 2009Co-Authors: Nathalie Faumont, Aurélie Chanut, Alan Benard, Nadine Cogné, Georges Delsol, Jean Feuillard, Fabienne MeggettoAbstract:BACKGROUND: In Epstein-Barr virus-associated Hodgkin's lymphomas, neoplastic Reed-Sternberg Cells and surrounding non-tumor B-Cells contain different variants of the LMP1-BNLF1 oncogene. In this study, we raised the question of functional properties of latent membrane protein 1 (LMP1) natural variants from both Reed-Sternberg and non-tumor B-Cells. DESIGN AND METHODS: Twelve LMP1 natural variants from Reed-Sternberg Cells, non-tumor B-Cells of Hodgkin's lymphomas and from B-Cells of benign reactive lymph nodes were cloned, sequenced and stably transfected in murine recombinant interleukin-3-dependent Ba/F3 Cells to search for relationships between LMP1 Cellular origin and oncogenic properties as well as nuclear factor-kappaB activation, and apoptosis protection. RESULTS: LMP1 variants of Reed-Sternberg Cell origin were often associated with increased mutation rate and with recurrent genetic events, such as del15bp associated with S to N replacement at codon 309, and four substitutions I85L, F106Y, I122L, and M129I. Oncogenic potential (growth factor-independence plus clonogenicity) was consistently associated with LMP1 variants from Reed-Sternberg Cells, but inconstantly for LMP1-variants from non-tumor B-Cells. Analysis of LMP1 variants from both normal B-Cells and Reed-Sternberg Cells indicates that protection against apoptosis through activation of nuclear factor-kappaB - whatever the Cellular origin of LMP1 - was maintained intact, regardless of the mutational pattern. CONCLUSIONS: Taken together, our results demonstrate that preserved nuclear factor-kappaB activity and protection against apoptosis would be the minimal prerequisites for all LMP1 natural variants from both normal and tumor Cells in Hodgkin's lymphomas, and that oncogenic potential would constitute an additional feature for LMP1 natural variants in Reed-Sternberg Cells.
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Comparative analysis of oncogenic properties and nuclear factor-κB activity of latent membrane protein 1 natural variants from Hodgkin’s lymphoma’s Reed-Sternberg Cells and normal B-lymphocytes
Haematologica, 2009Co-Authors: Nathalie Faumont, Aurélie Chanut, Alan Benard, Nadine Cogné, Georges Delsol, Jean Feuillard, Fabienne MeggettoAbstract:Background In Epstein-Barr virus-associated Hodgkin’s lymphomas, neoplastic Reed-Sternberg Cells and surrounding non-tumor B-Cells contain different variants of the LMP1-BNLF1 oncogene. In this study, we raised the question of functional properties of latent membrane protein 1 (LMP1) natural variants from both Reed-Sternberg and non-tumor B-Cells. Design and Methods Twelve LMP1 natural variants from Reed-Sternberg Cells, non-tumor B-Cells of Hodgkin’s lymphomas and from B-Cells of benign reactive lymph nodes were cloned, sequenced and stably transfected in murine recombinant interleukin-3-dependent Ba/F3 Cells to search for relationships between LMP1 Cellular origin and oncogenic properties as well as nuclear factor-κB activation, and apoptosis protection. Results LMP1 variants of Reed-Sternberg Cell origin were often associated with increased mutation rate and with recurrent genetic events, such as del15bp associated with S to N replacement at codon 309, and four substitutions I85L, F106Y, I122L, and M129I. Oncogenic potential (growth factor-independence plus clonogenicity) was consistently associated with LMP1 variants from Reed-Sternberg Cells, but inconstantly for LMP1-variants from non-tumor B-Cells. Analysis of LMP1 variants from both normal B-Cells and Reed-Sternberg Cells indicates that protection against apoptosis through activation of nuclear factor-κB - whatever the Cellular origin of LMP1 - was maintained intact, regardless of the mutational pattern. Conclusions Taken together, our results demonstrate that preserved nuclear factor-κB activity and protection against apoptosis would be the minimal prerequisites for all LMP1 natural variants from both normal and tumor Cells in Hodgkin’s lymphomas, and that oncogenic potential would constitute an additional feature for LMP1 natural variants in Reed-Sternberg Cells.