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 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

Abstract 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 Pleiotropic effects of the CD30 ligand on CD30-expressing cells and lymphoma cell lines

Blood ◽  
1994 ◽  
Vol 83 (8) ◽  
pp. 2045-2056 ◽  
Author(s):  
HJ Gruss ◽  
N Boiani ◽  
DE Williams ◽  
RJ Armitage ◽  
CA Smith ◽  
...  
Keyword(s):  
T Cell ◽  
B Cell ◽  
Cell Lines ◽  
Hodgkin's Disease ◽  
Hodgkin’S Disease ◽  
Lymphoma Cell ◽  
Leukemia Cell Line ◽  
Ligand Interaction ◽  
Anaplastic Lymphoma ◽  
Hodgkin's Lymphomas

Abstract CD30 is a member of the tumor necrosis factor receptor superfamily. CD30 was originally described as a cell surface antigen on primary and cultured Hodgkin's and Reed-Sternberg cells. In this study, recombinant human CD30 ligand was expressed on the surface of CV-1/EBNA cells and tested for biologic activities on a variety of different CD30+ human lymphoma cell lines. CD30 ligand enhanced Ig secretion of Epstein-Barr virus (EBV)-immortalized, CD30+ lymphoblastoid B-cell lines, but not Burkitt lymphoma lines. Recombinant CD30 ligand enhanced proliferation of “T-cell-like” Hodgkin's disease-derived cell lines and an adult T- cell leukemia cell line, but not “B-cell-like” Hodgkin's disease- derived cell lines, CD30+, EBV-immortalized lymphoblastoid B-cell lines, or CD30+ and EBV+ tumor B-cell non-Hodgkin's lymphoma cell lines. In addition, CD30 ligand mediated reduction of proliferation and viability, by induction of cytolytic cell death, of CD30+, large-cell anaplastic lymphoma cell lines. Two new antibodies, M44 and M67, against the CD30 antigen demonstrated similar biologic activities to the CD30 ligand. Taken together, these data demonstrate pleiotropic biologic activities of the CD30 ligand on different CD30+ lymphoma cell lines and indicate that the CD30-CD30 ligand interaction might have a pathophysiologic role in Hodgkin's and some non-Hodgkin's lymphomas.

scholarly journals Pleiotropic effects of the CD30 ligand on CD30-expressing cells and lymphoma cell lines

Blood ◽  
1994 ◽  
Vol 83 (8) ◽  
pp. 2045-2056 ◽  
Author(s):  
HJ Gruss ◽  
N Boiani ◽  
DE Williams ◽  
RJ Armitage ◽  
CA Smith ◽  
...  
Keyword(s):  
T Cell ◽  
B Cell ◽  
Cell Lines ◽  
Hodgkin's Disease ◽  
Hodgkin’S Disease ◽  
Lymphoma Cell ◽  
Leukemia Cell Line ◽  
Ligand Interaction ◽  
Anaplastic Lymphoma ◽  
Hodgkin's Lymphomas

CD30 is a member of the tumor necrosis factor receptor superfamily. CD30 was originally described as a cell surface antigen on primary and cultured Hodgkin's and Reed-Sternberg cells. In this study, recombinant human CD30 ligand was expressed on the surface of CV-1/EBNA cells and tested for biologic activities on a variety of different CD30+ human lymphoma cell lines. CD30 ligand enhanced Ig secretion of Epstein-Barr virus (EBV)-immortalized, CD30+ lymphoblastoid B-cell lines, but not Burkitt lymphoma lines. Recombinant CD30 ligand enhanced proliferation of “T-cell-like” Hodgkin's disease-derived cell lines and an adult T- cell leukemia cell line, but not “B-cell-like” Hodgkin's disease- derived cell lines, CD30+, EBV-immortalized lymphoblastoid B-cell lines, or CD30+ and EBV+ tumor B-cell non-Hodgkin's lymphoma cell lines. In addition, CD30 ligand mediated reduction of proliferation and viability, by induction of cytolytic cell death, of CD30+, large-cell anaplastic lymphoma cell lines. Two new antibodies, M44 and M67, against the CD30 antigen demonstrated similar biologic activities to the CD30 ligand. Taken together, these data demonstrate pleiotropic biologic activities of the CD30 ligand on different CD30+ lymphoma cell lines and indicate that the CD30-CD30 ligand interaction might have a pathophysiologic role in Hodgkin's and some non-Hodgkin's lymphomas.

Large-cell anaplastic lymphoma-specific translocation in Hodgkin's disease

The Lancet ◽  
1995 ◽  
Vol 345 (8954) ◽  
pp. 918-921 ◽  
Author(s):  
JamesR Downing ◽  
Marc Ladanyi ◽  
Mark Raffeld ◽  
LawrenceM Weiss ◽  
StephanW Morris ◽  
...  
Keyword(s):  
Hodgkin's Disease ◽  
Hodgkin’S Disease ◽  
Large Cell ◽  
Anaplastic Lymphoma

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 The expression of the Hodgkin's disease associated antigen Ki-1 in reactive and neoplastic lymphoid tissue: evidence that Reed-Sternberg cells and histiocytic malignancies are derived from activated lymphoid cells

Blood ◽  
1985 ◽  
Vol 66 (4) ◽  
pp. 848-858 ◽  
Author(s):  
H Stein ◽  
DY Mason ◽  
J Gerdes ◽  
N O'Connor ◽  
J Wainscoat ◽  
...  
Keyword(s):  
T Cell ◽  
B Cell ◽  
Hodgkin's Disease ◽  
Hodgkin’S Disease ◽  
Lymphoid Cells ◽  
Cell Phenotype ◽  
Cell Type ◽  
Lymphomatoid Papulosis ◽  
T Cell Lymphomas ◽  
Immunoblastic Lymphadenopathy

Abstract Ki-1 is a monoclonal antibody (raised against a Hodgkin's disease- derived cell line) that, in biopsy tissue affected by Hodgkin's disease, reacts selectively with Reed-Sternberg cells. The expression of Ki-1 antigen has been analyzed by immunocytochemical techniques in a wide range of human tissue and cell samples, including fetal tissue, malignant lymphomas (290 cases), and mitogen- and virus-transformed peripheral blood lymphocytes. The antigen was detectable on a variable proportion of cells in all cases of lymphomatoid papulosis and angio- immunoblastic lymphadenopathy and in 28% of the cases of peripheral T cell lymphomas (including lympho-epithelioid lymphomas). It was also expressed (more strongly) on tumor cells in 45 cases of diffuse large- cell lymphoma, most of which had originally been diagnosed as malignant histiocytosis or anaplastic carcinoma, because of their bizarre morphology. However, all of these cases lacked macrophage and epithelial antigens. Thirty-five cases expressed T cell-related antigens (associated in nine cases with the coexpression of B cell- related antigens), seven bore B cell-related antigens alone, and three were devoid of T and B cell markers. DNA hybridization with a JH specific probe showed a germline configuration in 11 cases of T cell phenotype, in two cases lacking T and B cell antigens, and in one case of mixed T/B phenotype, while rearrangement was found in two cases of clear B cell type and in one mixed T/B case. Expression of the Ki-1 antigen could be induced, together with interleukin 2 (IL 2) receptor, on normal lymphoid cells of both T and B cell type by exposure to phytohemagglutinin, human T leukemia viruses, Epstein-Barr virus, or Staphylococcus aureus. The results obtained indicate that Ki-1 antigen is an inducible lymphoid-associated molecule that identifies a group of hitherto poorly characterized normal and neoplastic large lymphoid cells. Tumors comprised solely of these cells show both morphological and immunological similarities to the neoplastic cells in Hodgkin's disease. This suggests that both disorders represent the neoplastic proliferation of activated lymphoid cells of either T cell or, less commonly, B cell origin. Disorders in which only a minority of cells express Ki-1 antigen (lymphomatoid papulosis, angio-immunoblastic lymphadenopathy, and certain T cell lymphomas) probably represent lesions in which only some of the abnormal cells have transformed into an “activation state.” In direct support of this view is the finding that the Ki-1 expression in these lesions is accompanied by the expression of HLA-DR and IL 2 receptors.

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 IL-2– and IL-15–induced activation of the rapamycin-sensitive mTORC1 pathway in malignant CD4+ T lymphocytes

Blood ◽  
2008 ◽  
Vol 111 (4) ◽  
pp. 2181-2189 ◽  
Author(s):  
Michal Marzec ◽  
Xiaobin Liu ◽  
Monika Kasprzycka ◽  
Agnieszka Witkiewicz ◽  
Puthiyaveettil N. Raghunath ◽  
...  
Keyword(s):  
T Cell ◽  
Cell Lines ◽  
Cell Transformation ◽  
Single Agent ◽  
Large Cell ◽  
Dependent Manner ◽  
T Cell Lymphomas ◽  
Mtorc1 Signaling ◽  
Mtorc1 Pathway ◽  
Mtorc1 Activation

We examined functional status, activation mechanisms, and biologic role of the mTORC1 signaling pathway in malignant CD4+ T cells derived from the cutaneous T-cell lymphoma (CTCL). Whereas the spontaneously growing CTCL-derived cell lines displayed persistent activation of the TORC1 as well as the PI3K/Akt and MEK/ERK pathways, the IL-2–dependent cell lines activated the pathways in response to IL-2 and IL-15 but not IL-21. Activation of mTORC1 and MEK/ERK was nutrient dependent. The mTORC1, PI3K/Akt, and MEK/ERK pathways could also be activated by IL-2 in the primary leukemic, mitogen-preactivated CTCL cells. mTORC1 activation was also detected in the CTCL tissues in the lymphoma stage–dependent manner with the highest percentage of positive cells present in the cases with a large cell transformation. Rapamycin inhibited mTORC1 signaling and suppressed CTCL cell proliferation but showed little effect on their apoptotic rate when used as a single agent. Activation of the mTORC1, PI3K/Akt, and MEK/ERK pathways was strictly dependent on the Jak3 and Jak1 kinases. Finally, mTORC1 activation was transduced preferentially through the PI3K/Akt pathway. These findings document the selective γc-signaling cytokine-mediated activation of the mTORC1 pathway in the CTCL cells and suggest that the pathway represents a therapeutic target in CTCL and, possibly, other T-cell lymphomas.

scholarly journals Therapies for Peripheral T-Cell Lymphomas

Hematology ◽  
2011 ◽  
Vol 2011 (1) ◽  
pp. 515-524 ◽  
Author(s):  
Kerry J. Savage
Keyword(s):  
T Cell ◽  
Cell Lymphoma ◽  
Treatment Strategies ◽  
Large Cell ◽  
Cure Rate ◽  
Limited Evidence ◽  
Anaplastic Lymphoma ◽  
T Cell Lymphomas ◽  
Histologic Subtypes ◽  
Peripheral T Cell Lymphomas

AbstractPeripheral T-cell lymphomas (PTCLs) are a rare and heterogeneous group of disorders that, for the most part, are associated with a very poor prognosis. The standard therapy for PTCLs is CHOP (cyclophosphamide, doxorubicin, vincristine, and prednisone) or a comparable CHOP-like regimen that incorporates anthracyclines. With the exception of anaplastic lymphoma kinase–positive anaplastic large cell lymphoma (ALK+ ALCL), the cure rate for PTCLs with CHOP is low, and limited evidence suggests that anthracyclines do not improve the prognosis. However, there is no compelling evidence that any other regimen or approach is superior. It remains challenging to compare alternative therapies or treatment strategies with CHOP because the majority of data are retrospective and include diverse patient populations. Recently, prospective studies have been initiated exclusively for PTCL, and in some, select histologic subtypes are evaluated in an effort to remove heterogeneity. Encouragingly, there have been several new therapies emerging with activity in PTCLs and exciting novel combinations under consideration that will hopefully move the field forward and improve outcome in this challenging group of diseases.

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