scholarly journals ALK gene products in anaplastic large cell lymphomas and Hodgkin's disease

Blood ◽  
1995 ◽  
Vol 86 (5) ◽  
pp. 1694-1700 ◽  
Author(s):  
H Herbst ◽  
J Anagnostopoulos ◽  
B Heinze ◽  
H Durkop ◽  
M Hummel ◽  
...  
Keyword(s):  
Cell Lines ◽  
Hodgkin's Disease ◽  
Fusion Gene ◽  
Hodgkin’S Disease ◽  
Young Patients ◽  
Large Cell ◽  
Common Type ◽  
Gene Products ◽  
Cytogenetic Analyses

The translocation t(2;5)(p23;q35), discovered in CD30+ anaplastic large cell (ALC) lymphomas, creates a potentially oncogenic fusion gene, part of which is contributed by a novel tyrosine kinase, ALK. Absence of ALK expression from normal hematolymphoid cells provides a basis for the morphologic assessment of t(2;5). The distribution of the t(2;5) in ALC lymphomas and Hodgkin's disease (HD), as assayed by nonmorphologic methods, is controversial. We used in situ hybridization and/or immunohistology to show ALK gene products in 85 ALC lymphomas, 82 HD cases, 40 other lymphoproliferations, as well as in 6 HD- and 4 ALC lymphoma-derived cell lines. ALK gene products were restricted to t(2;5)-positive ALC lymphoma cell lines and tumor cells of 16 primary non-B cell, common-type ALC lymphomas. These were mainly from young patients with initial lymphonodal disease. ALK expression was not detectable in any other specimen, including all cases of HD and HD-like type ALC lymphoma as well as secondary ALC lymphomas. Full congruence was noted for labeling results obtained with both methods. In agreement with cytogenetic analyses, but at variance with recently published studies, ALK gene expression distinguishes a subset of ALC lymphomas from other CD30+ lymphomas, including HD. The results do not support concepts attributing a significant role to the t(2;5) in the development of HD.

scholarly journals Demonstration of monoclonal EBV genomes in Hodgkin's disease and Ki-1- positive anaplastic large cell lymphoma by combined Southern blot and in situ hybridization [see comments]

Blood ◽  
1989 ◽  
Vol 74 (2) ◽  
pp. 810-816 ◽  
Author(s):  
I Anagnostopoulos ◽  
H Herbst ◽  
G Niedobitek ◽  
H Stein
Keyword(s):  
In Situ Hybridization ◽  
Hodgkin's Disease ◽  
Hodgkin’S Disease ◽  
Large Cell ◽  
Viral Genomes ◽  
Barr Virus ◽  
Infected Cells ◽  
Epstein Barr ◽  
Distinct Morphology

Abstract Forty-two cases of Hodgkin's disease (HD) and 22 cases of Ki-1-positive anaplastic large cell (Ki-1 + ALC) lymphoma were examined by Southern blotting for the presence of Epstein-Barr virus (EBV) DNA. Seven cases of HD and one case of Ki-1 + ALC lymphoma scored positive with a probe specific for the internal repetitive region of the EBV genome. Subsequently, these viral genomes could be demonstrated to be monoclonal in origin using an EBV terminal region DNA probe. In situ hybridization revealed that in two HD cases, the EBV infected cells had the distinct morphology of Hodgkin and Reed-Sternberg cells, thus suggesting a direct pathoetiological relationship between EBV and some cases of HD.

scholarly journals Expression of functional CD40 antigen on Reed-Sternberg cells and Hodgkin's disease cell lines

Blood ◽  
1995 ◽  
Vol 85 (3) ◽  
pp. 780-789 ◽  
Author(s):  
A Carbone ◽  
A Gloghini ◽  
V Gattei ◽  
D Aldinucci ◽  
M Degan ◽  
...  
Keyword(s):  
Flow Cytometry ◽  
Cell Lines ◽  
Hodgkin's Disease ◽  
Hodgkin’S Disease ◽  
Growth Factor Receptor ◽  
Large Cell ◽  
Distinct Pattern ◽  
Histologic Subtype ◽  
Hodgkin's Lymphomas

CD40 is a member of the nerve growth factor receptor family, showing a significant homology to the Hodgkin's disease (HD)-associated antigen CD30 and is capable of transduce growth signals in a number of cell types. A series of 312 lymphoma samples, including 139 cases of HD, 32 cases of CD30+ anaplastic large cell (ALC) lymphomas, 141 cases of other non-Hodgkin's lymphomas (NHLs), and a panel of HD- or NHL-derived cell lines, were evaluated for CD40 expression by immunostaining of paraffin embedded sections, cell smears and flow cytometry. CD40 was strongly expressed with a highly distinct pattern of staining on Reed- Sternberg (RS) cells and variants in 100% (139/139) of HD cases, irrespective of their antigenic phenotype (T, B, non T-non B) and histologic subtype of HD. Conversely, CD40 was immunodetected on only one third (12/32; 37%) of ALC lymphoma cases and on 105 of 127 B-cell NHLs. The relative cell density of CD40 on HD cell lines (L-428, KM-H2, HDLM-2) as assessed by flow cytometry was significantly higher than on all other lymphoma cells analyzed. Engagement of CD40 by its soluble ligand (CD40L) enhanced both clonogenic capacity and colony cell survival of HD cell lines. Such effect was potentiated by interleukin-9 costimulation in KM-H2 cells. Finally, we have shown that in vitro rosetting of activated CD4+ T cells to HD cells (L-428) is mediated in part by the CD40/CD40L adhesion pathway. Our data indicate that CD40 is a useful antigen for immunodetection and identification of tumor cells in all subtypes of HD, and suggest that it may play a role in the regulation of RS cell expansion and the contact-dependent interactions of these cells with cytokine-producing T lymphocytes.

scholarly journals Expression of interleukin-6 and interleukin-6 receptor in Hodgkin's disease

Blood ◽  
1991 ◽  
Vol 77 (11) ◽  
pp. 2413-2418 ◽  
Author(s):  
M Jucker ◽  
H Abts ◽  
W Li ◽  
R Schindler ◽  
H Merz ◽  
...  
Keyword(s):  
Cell Lines ◽  
Interleukin 6 ◽  
Hodgkin's Disease ◽  
Northern Blot Analysis ◽  
Acute Phase Proteins ◽  
Hodgkin’S Disease ◽  
Interleukin 6 Receptor ◽  
Dependent Cell ◽  
Culture Supernatants

Interleukin-6 (IL-6) is a multipotent lymphokine that can mediate differentiation of B cells into Ig-secreting cells, stimulate the growth of plasmacytomas, hybridomas, and T cells, and induce acute- phase proteins in liver cells. It has been suggested that IL-6 is involved in the pathogenesis of several diseases by autocrine or paracrine pathways. To examine whether IL-6 is possibly involved in the pathophysiology of Hodgkin's disease (HD), we analyzed the expression of IL-6 and IL-6 receptor mRNA and protein in cell lines and primary specimens from patients with HD. IL-6-specific transcripts were detected in three of six HD-derived cell lines by Northern blot analysis. In the culture supernatants of four HD-derived cell lines, IL- 6 was detected by radioimmunoassay. Biologic activity of IL-6 was confirmed by proliferation of an IL-6-dependent cell line. In situ hybridization experiments showed IL-6-specific transcripts in Hodgkin (H) and Reed-Sternberg (RS) cells in primary tissues of two patients. In addition, mRNAs specific for the IL-6 receptor were detected in five HD-derived cell lines. Immunostaining experiments showed expression of IL-6 receptor molecules on H and RS cells in 8 of 16 cases with HD. Thus, our data suggest that IL-6 might be involved in the pathophysiology of HD.

scholarly journals Transcripts of the npm-alk fusion gene in anaplastic large cell lymphoma, Hodgkin's disease, and reactive lymphoid lesions

Blood ◽  
1995 ◽  
Vol 86 (9) ◽  
pp. 3517-3521 ◽  
Author(s):  
PG Elmberger ◽  
MD Lozano ◽  
DD Weisenburger ◽  
W Sanger ◽  
WC Chan
Keyword(s):  
Anaplastic Large Cell Lymphoma ◽  
Hodgkin's Disease ◽  
Fusion Gene ◽  
Cell Lymphoma ◽  
Cytogenetic Study ◽  
Hodgkin’S Disease ◽  
Large Cell ◽  
Rt Pcr ◽  
Anaplastic Lymphoma ◽  
Large Cell Lymphoma

Anaplastic large cell lymphoma (ALCL) and Hodgkin's disease (HD) have some pathologic and immunohistochemical similarities, and a histogenetic relationship between them has been suggested by some investigators. By cytogenetic study, the t(2;5)(p23;q35) translocation appears to be unique for ALCL. The breakpoints of the t(2;5)(p23;q35) have recently been cloned and are reported to involve a novel tyrosine kinase gene, anaplastic lymphoma kinase (alk), on chromosome 2 and the nucleophosmin gene (npm) on chromosome 5. Therefore, we studied the frequency of npm-alk translocation in ALCL using a reverse transcriptase-polymerase chain reaction (RT-PCR) assay. We also studied HD and a variety of reactive lymphoid lesions since there is contradictory information in the literature on the occurrence of the npm-alk rearrangement in HD. We detected npm-alk hybrid mRNA in 8 of 22 cases of ALCL (36%), but none of the 21 cases of HD or the 11 cases with reactive lesions contained amplifiable template. All positive ALCL had the T or indeterminate phenotype and occurred in young adults or children. There was very good correlation between a cytogenetically detectable t(2;5) and a positive signal by RT-PCR. Our results indicate a selective but relatively infrequent association between the t(2;5) and ALCL of T or indeterminate phenotype, not shared with HD or reactive hyperplasia.

scholarly journals In situ demonstration of Epstein-Barr virus small RNAs (EBER 1) in acquired immunodeficiency syndrome-related lymphomas: correlation with tumor morphology and primary site

Blood ◽  
1993 ◽  
Vol 82 (2) ◽  
pp. 619-624 ◽  
Author(s):  
SJ Hamilton-Dutoit ◽  
M Raphael ◽  
J Audouin ◽  
J Diebold ◽  
I Lisse ◽  
...  
Keyword(s):  
Tumor Cells ◽  
Hodgkin's Disease ◽  
Epstein Barr Virus ◽  
Hodgkin’S Disease ◽  
Large Cell ◽  
Barr Virus ◽  
Acquired Immunodeficiency ◽  
Epstein Barr ◽  
Immunodeficiency Syndrome

Abstract Some acquired immunodeficiency syndrome (AIDS)-related lymphomas (ARLs) are infected with Epstein-Barr virus (EBV), although the frequency and importance of this association is disputed. Using paraffin section RNA in situ hybridization (ISH) with digoxigenin-labeled riboprobes, we screened 16 central nervous system (CNS) non-Hodgkin's lymphomas (NHLs), 101 systemic NHLs, and 11 Hodgkin's disease cases arising in human immunodeficiency virus-seropositive individuals for EBV-encoded small RNA (EBER 1) expression, an EBV gene product transcribed in abundance during latent infection. Tumor cells contained EBV in 85 of 128 ARLs (66%), but infection rates differed with lymphoma type. EBER 1 was expressed in tumor cells in 11 of 11 Hodgkin's disease cases (100%), 15 of 16 CNS NHLs (94%), and 46 of 60 systemic immunoblast- rich/large-cell lymphomas (77%), but in only 12 of 35 Burkitt-type (small noncleaved cell) (34%) and 1 of 6 monomorphic centroblastic (diffuse large noncleaved cell) (17%) lymphomas. In most EBV-positive ARLs, all recognizable viable tumor cells expressed EBER 1. We conclude that (1) EBV infects tumor cells in all AIDS-related Hodgkin's disease cases, in virtually all primary CNS ARLs, and in most systemic immunoblast-rich/large-cell ARLs; (2) only a minority of Burkitt-type and monomorphic centroblastic lymphomas are associated with EBV; and (3) EBER-ISH is ideal for the histopathologic detection of latent EBV in routine tissue specimens.

scholarly journals In situ demonstration of Epstein-Barr virus small RNAs (EBER 1) in acquired immunodeficiency syndrome-related lymphomas: correlation with tumor morphology and primary site

Blood ◽  
1993 ◽  
Vol 82 (2) ◽  
pp. 619-624 ◽  
Author(s):  
SJ Hamilton-Dutoit ◽  
M Raphael ◽  
J Audouin ◽  
J Diebold ◽  
I Lisse ◽  
...  
Keyword(s):  
Tumor Cells ◽  
Hodgkin's Disease ◽  
Epstein Barr Virus ◽  
Hodgkin’S Disease ◽  
Large Cell ◽  
Barr Virus ◽  
Acquired Immunodeficiency ◽  
Epstein Barr ◽  
Immunodeficiency Syndrome

Some acquired immunodeficiency syndrome (AIDS)-related lymphomas (ARLs) are infected with Epstein-Barr virus (EBV), although the frequency and importance of this association is disputed. Using paraffin section RNA in situ hybridization (ISH) with digoxigenin-labeled riboprobes, we screened 16 central nervous system (CNS) non-Hodgkin's lymphomas (NHLs), 101 systemic NHLs, and 11 Hodgkin's disease cases arising in human immunodeficiency virus-seropositive individuals for EBV-encoded small RNA (EBER 1) expression, an EBV gene product transcribed in abundance during latent infection. Tumor cells contained EBV in 85 of 128 ARLs (66%), but infection rates differed with lymphoma type. EBER 1 was expressed in tumor cells in 11 of 11 Hodgkin's disease cases (100%), 15 of 16 CNS NHLs (94%), and 46 of 60 systemic immunoblast- rich/large-cell lymphomas (77%), but in only 12 of 35 Burkitt-type (small noncleaved cell) (34%) and 1 of 6 monomorphic centroblastic (diffuse large noncleaved cell) (17%) lymphomas. In most EBV-positive ARLs, all recognizable viable tumor cells expressed EBER 1. We conclude that (1) EBV infects tumor cells in all AIDS-related Hodgkin's disease cases, in virtually all primary CNS ARLs, and in most systemic immunoblast-rich/large-cell ARLs; (2) only a minority of Burkitt-type and monomorphic centroblastic lymphomas are associated with EBV; and (3) EBER-ISH is ideal for the histopathologic detection of latent EBV in routine tissue specimens.

scholarly journals Interleukin-9 expression in human malignant lymphomas: unique association with Hodgkin's disease and large cell anaplastic lymphoma

Blood ◽  
1991 ◽  
Vol 78 (5) ◽  
pp. 1311-1317 ◽  
Author(s):  
H Merz ◽  
FA Houssiau ◽  
K Orscheschek ◽  
JC Renauld ◽  
A Fliedner ◽  
...  
Keyword(s):  
T Cell ◽  
Growth Factor ◽  
Cell Lines ◽  
Hodgkin's Disease ◽  
Hodgkin’S Disease ◽  
Large Cell ◽  
Anaplastic Lymphoma ◽  
T Cell Lymphomas ◽  
Interleukin 9 ◽  
Unique Association

To test the possibility that interleukin-9 (IL-9), the human homologue of the mouse T-cell growth factor P40, may be involved in the pathogenesis of human lymphomas, we examined IL-9 expression in a variety of tumors both by Northern blot analysis and by in situ hybridization. Of 18 B-cell non-Hodgkin's lymphomas and 11 peripheral T- cell lymphomas, none expressed IL-9 message. By contrast, IL-9 message was found in two of six cases of large cell anaplastic lymphoma (LCAL) and in 6 of 13 cases of Hodgkin's disease (HD). In HD the strongest signals were observed in Hodgkin (H) and Sternberg-Reed (SR) cells, but IL-9 mRNA was also detected in small lymphocytic cells. A search for IL- 9 message in a panel of 20 cell lines derived both from hematopoietic and nonhematopoietic tumors confirmed the unique association of IL-9 expression with HD and LCAL in as much as the only two cell lines with IL-9 message were derived from cases of HD and LCAL. These results suggest that IL-9 is not involved as an autocrine growth factor in the pathogenesis of most B- and T-cell lymphomas, but that it may play a role in HD and LCAL.

scholarly journals Demonstration of monoclonal EBV genomes in Hodgkin's disease and Ki-1- positive anaplastic large cell lymphoma by combined Southern blot and in situ hybridization [see comments]

Blood ◽  
1989 ◽  
Vol 74 (2) ◽  
pp. 810-816 ◽  
Author(s):  
I Anagnostopoulos ◽  
H Herbst ◽  
G Niedobitek ◽  
H Stein
Keyword(s):  
In Situ Hybridization ◽  
Hodgkin's Disease ◽  
Hodgkin’S Disease ◽  
Large Cell ◽  
Viral Genomes ◽  
Barr Virus ◽  
Infected Cells ◽  
Epstein Barr ◽  
Distinct Morphology

Forty-two cases of Hodgkin's disease (HD) and 22 cases of Ki-1-positive anaplastic large cell (Ki-1 + ALC) lymphoma were examined by Southern blotting for the presence of Epstein-Barr virus (EBV) DNA. Seven cases of HD and one case of Ki-1 + ALC lymphoma scored positive with a probe specific for the internal repetitive region of the EBV genome. Subsequently, these viral genomes could be demonstrated to be monoclonal in origin using an EBV terminal region DNA probe. In situ hybridization revealed that in two HD cases, the EBV infected cells had the distinct morphology of Hodgkin and Reed-Sternberg cells, thus suggesting a direct pathoetiological relationship between EBV and some cases of HD.

scholarly journals Expression of interleukin-6 and interleukin-6 receptor in Hodgkin's disease

Blood ◽  
1991 ◽  
Vol 77 (11) ◽  
pp. 2413-2418 ◽  
Author(s):  
M Jucker ◽  
H Abts ◽  
W Li ◽  
R Schindler ◽  
H Merz ◽  
...  
Keyword(s):  
Cell Lines ◽  
Interleukin 6 ◽  
Hodgkin's Disease ◽  
Northern Blot Analysis ◽  
Acute Phase Proteins ◽  
Hodgkin’S Disease ◽  
Interleukin 6 Receptor ◽  
Dependent Cell ◽  
Culture Supernatants

Abstract Interleukin-6 (IL-6) is a multipotent lymphokine that can mediate differentiation of B cells into Ig-secreting cells, stimulate the growth of plasmacytomas, hybridomas, and T cells, and induce acute- phase proteins in liver cells. It has been suggested that IL-6 is involved in the pathogenesis of several diseases by autocrine or paracrine pathways. To examine whether IL-6 is possibly involved in the pathophysiology of Hodgkin's disease (HD), we analyzed the expression of IL-6 and IL-6 receptor mRNA and protein in cell lines and primary specimens from patients with HD. IL-6-specific transcripts were detected in three of six HD-derived cell lines by Northern blot analysis. In the culture supernatants of four HD-derived cell lines, IL- 6 was detected by radioimmunoassay. Biologic activity of IL-6 was confirmed by proliferation of an IL-6-dependent cell line. In situ hybridization experiments showed IL-6-specific transcripts in Hodgkin (H) and Reed-Sternberg (RS) cells in primary tissues of two patients. In addition, mRNAs specific for the IL-6 receptor were detected in five HD-derived cell lines. Immunostaining experiments showed expression of IL-6 receptor molecules on H and RS cells in 8 of 16 cases with HD. Thus, our data suggest that IL-6 might be involved in the pathophysiology of HD.

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