scholarly journals Induction of the IL-9 gene by HTLV-I Tax stimulates the spontaneous proliferation of primary adult T-cell leukemia cells by a paracrine mechanism

Blood ◽  
2008 ◽  
Vol 111 (10) ◽  
pp. 5163-5172 ◽  
Author(s):  
Jing Chen ◽  
Mike Petrus ◽  
Bonita R. Bryant ◽  
Vinh Phuc Nguyen ◽  
Mindy Stamer ◽  
...  
Keyword(s):  
T Cells ◽  
T Cell ◽  
Ex Vivo ◽  
Proximal Promoter ◽  
Type I ◽  
Dependent Manner ◽  
T Cell Leukemia ◽  
Cell Leukemia ◽  
Adult T Cell Leukemia ◽  
Spontaneous Proliferation

AbstractThe etiologic agent of adult T-cell leukemia (ATL) is human T cell lymphotropic virus type I (HTLV-I). The HTLV-I protein Tax alters gene expression, including those of cytokines and their receptors, which plays an important role in early stages of ATL. Here we demonstrate that expression of interleukin-9 (IL-9) is activated by Tax via an NF-κB motif in its proximal promoter, whereas IL-9 receptor-α (IL-9Rα) expression is not induced by Tax. However, supporting a role for IL-9/IL-9Rα in ATL, a neutralizing monoclonal antibody directed toward IL-9Rα inhibited ex vivo spontaneous proliferation of primary ATL cells from several patients. Fluorescence-activated cell sorter analysis of freshly isolated peripheral blood mononuclear cells from these patients revealed high level expression of IL-9Rα on their CD14-expressing monocytes. Furthermore, purified T cells or monocytes alone from these patients did not proliferate ex vivo, whereas mixtures of these cell types manifested significant proliferation through a contact-dependent manner. Taken together, our data suggest that primary ATL cells, via IL-9, support the action of IL-9Rα/CD14-expressing monocytes, which subsequently support the ex vivo spontaneous proliferation of malignant T cells. In summary, these data support a role for IL-9 and its receptor in ATL by a paracrine mechanism.

scholarly journals Deregulation of microRNA involved in hematopoiesis and the immune response in HTLV-I adult T-cell leukemia

Blood ◽  
2009 ◽  
Vol 113 (20) ◽  
pp. 4914-4917 ◽  
Author(s):  
Marcia Bellon ◽  
Yves Lepelletier ◽  
Olivier Hermine ◽  
Christophe Nicot
Keyword(s):  
T Cell ◽  
Cell Lines ◽  
Ex Vivo ◽  
Type I ◽  
T Cell Leukemia ◽  
Cell Leukemia ◽  
Hematopoietic Stem ◽  
Adult T Cell Leukemia ◽  
Infected Cells

Human T-cell leukemia virus type-I (HTLV-I) is the etiologic agent of adult T-cell leukemia (ATL), an aggressive lymphoproliferative disease. MicroRNAs (miRNAs) are differentially expressed during hematopoiesis and lineage commitment of hematopoietic stem cell progenitors (HSCPs). Here, we report aberrant expression of hematopoietic-specific miR-223, miR-181a, miR-150, miR-142.3p, and miR-155 in HTLV-I–infected cells in vitro and uncultured ex vivo ATL cells. Our results suggest that HTLV-I–infected cells have an unbalanced expression of miRNA that favors T-cell differentiation. We also found altered expression of miRNA previously recognized as innate immunity regulators: miR-155, miR-125a, miR-132, and miR-146. Strikingly, our data also revealed significant differences between ex vivo ATL tumor cells and in vitro HTLV-I cell lines. Specifically, miR-150 and miR-223 were up-regulated in ATL patients but consistently down-regulated in HTLV-I cell lines, suggesting that ATL cells and in vitro–established cells are derived from distinct cellular populations.

scholarly journals Human T-cell leukemia virus type I Tax associates with and is negatively regulated by the NF-kappa B2 p100 gene product: implications for viral latency

1994 ◽  
Vol 14 (2) ◽  
pp. 1374-1382
Author(s):  
C Béraud ◽  
S C Sun ◽  
P Ganchi ◽  
D W Ballard ◽  
W C Greene
Keyword(s):  
T Cells ◽  
T Cell ◽  
Virus Type ◽  
Leukemia Virus ◽  
Type I ◽  
T Cell Leukemia ◽  
Cell Leukemia ◽  
Cell Leukemia Virus Type ◽  
Adult T Cell Leukemia ◽  
Human T Cell

Human T-cell leukemia virus type I (HTLV-I) is the etiologic agent of the adult T-cell leukemia, an aggressive and often fatal malignancy of activated human CD4 T cells. HTLV-I encodes an essential 40-kDa protein termed Tax that not only transactivates the long terminal repeat of this retrovirus but also induces an array of cellular genes. Tax-mediated transformation of T cells likely involves the deregulated expression of various cellular genes that normally regulate lymphocyte growth produced by altered activity of various endogenous host transcription factors. In particular, Tax is capable of modulating the expression or activity of various host transcription factors, including members of the NF-kappa B/Rel and CREB/ATF families, as well as the cellular factors HEB-1 and p67SRF. An additional distinguishing characteristic of HTLV-I infection is the profound state of viral latency that is present in circulating primary leukemic T cells. In this study, we demonstrate that HTLV-I Tax can physically associate with p100, the product of the Rel-related NF-kappa B2 gene, both in transfected cells and in HTLV-I-infected leukemic T-cell lines. Furthermore, the physical interaction of Tax with p100 leads to the inhibition of Tax-induced activation of the HTLV-I and human immunodeficiency virus type 1 long terminal repeats, reflecting p100-mediated cytoplasmic sequestration of the normally nuclearly expressed Tax protein. In contrast, a mutant of Tax that selectively fails to activate nuclear NF-kappa B expression does not associate with p100. Together, these results suggest that the cytoplasmic interplay of Tax and p100 may play an important role in the initiation and maintenance of HTLV-1 latency observed in adult T-cell leukemia.

scholarly journals Human T-cell leukemia virus type I Tax associates with and is negatively regulated by the NF-kappa B2 p100 gene product: implications for viral latency.

1994 ◽  
Vol 14 (2) ◽  
pp. 1374-1382 ◽  
Author(s):  
C Béraud ◽  
S C Sun ◽  
P Ganchi ◽  
D W Ballard ◽  
W C Greene
Keyword(s):  
T Cells ◽  
T Cell ◽  
Virus Type ◽  
Leukemia Virus ◽  
Type I ◽  
T Cell Leukemia ◽  
Cell Leukemia ◽  
Cell Leukemia Virus Type ◽  
Adult T Cell Leukemia ◽  
Human T Cell

Human T-cell leukemia virus type I (HTLV-I) is the etiologic agent of the adult T-cell leukemia, an aggressive and often fatal malignancy of activated human CD4 T cells. HTLV-I encodes an essential 40-kDa protein termed Tax that not only transactivates the long terminal repeat of this retrovirus but also induces an array of cellular genes. Tax-mediated transformation of T cells likely involves the deregulated expression of various cellular genes that normally regulate lymphocyte growth produced by altered activity of various endogenous host transcription factors. In particular, Tax is capable of modulating the expression or activity of various host transcription factors, including members of the NF-kappa B/Rel and CREB/ATF families, as well as the cellular factors HEB-1 and p67SRF. An additional distinguishing characteristic of HTLV-I infection is the profound state of viral latency that is present in circulating primary leukemic T cells. In this study, we demonstrate that HTLV-I Tax can physically associate with p100, the product of the Rel-related NF-kappa B2 gene, both in transfected cells and in HTLV-I-infected leukemic T-cell lines. Furthermore, the physical interaction of Tax with p100 leads to the inhibition of Tax-induced activation of the HTLV-I and human immunodeficiency virus type 1 long terminal repeats, reflecting p100-mediated cytoplasmic sequestration of the normally nuclearly expressed Tax protein. In contrast, a mutant of Tax that selectively fails to activate nuclear NF-kappa B expression does not associate with p100. Together, these results suggest that the cytoplasmic interplay of Tax and p100 may play an important role in the initiation and maintenance of HTLV-1 latency observed in adult T-cell leukemia.

scholarly journals Evidence for the interleukin-2 dependent expansion of leukemic cells in adult T cell leukemia

Blood ◽  
1987 ◽  
Vol 70 (5) ◽  
pp. 1407-1411 ◽  
Author(s):  
M Maeda ◽  
N Arima ◽  
Y Daitoku ◽  
M Kashihara ◽  
H Okamoto ◽  
...  
Keyword(s):  
T Cell ◽  
Receptor Gene ◽  
Interleukin 2 ◽  
Leukemic Cells ◽  
Type I ◽  
T Cell Leukemia ◽  
Cell Leukemia ◽  
In Vitro Proliferation ◽  
Adult T Cell Leukemia

Abstract Interleukin 2 (IL-2) receptor/Tac antigen is abnormally expressed on cells of patients with adult T cell leukemia (ATL) caused by infection with human T lymphotropic virus type I (HTLV-I). Twenty-five patients with ATL were examined to determine whether their leukemic cells continued to show IL-2-dependent proliferation. In 21 patients, the in vitro proliferation of HTLV-I-infected nonleukemic T cell clones was found to be dependent on IL-2. However, clonality analysis based on T cell receptor gene rearrangement profiles and the site of HTLV-I provirus integration revealed IL-2-dependent growth in leukemic cells in four patients with ATL. These results provide evidence for the IL-2- dependent proliferation of leukemic cells in some ATL patients.

Human T-cell lymphotropic virus type I (HTLV-I) antibodies in pre-diagnostic serum of patients with familial adult T-cell leukemia/lymphoma (ATL)

2006 ◽  
Vol 8 (3) ◽  
pp. 169-176 ◽  
Author(s):  
Abraham M. Y. Nomura ◽  
Eugene T. Yanagihara ◽  
William A. Blattner ◽  
Gloria Y. F. Ho ◽  
Melvin S. Inamasu ◽  
...  
Keyword(s):  
T Cell ◽  
Virus Type ◽  
Type I ◽  
T Cell Leukemia ◽  
Cell Leukemia ◽  
Adult T Cell Leukemia ◽  
Human T Cell

The tumor marker Fascin is strongly induced by the Tax oncoprotein of HTLV-1 through NF-κB signals

Blood ◽  
2011 ◽  
Vol 117 (13) ◽  
pp. 3609-3612 ◽  
Author(s):  
Andrea K. Kress ◽  
Martina Kalmer ◽  
Aileen G. Rowan ◽  
Ralph Grassmann ◽  
Bernhard Fleckenstein
Keyword(s):  
T Cells ◽  
T Cell ◽  
Tumor Marker ◽  
Cd4 T Cells ◽  
Initial Step ◽  
T Cell Leukemia ◽  
Cell Leukemia ◽  
Viral Oncoprotein ◽  
Adult T Cell Leukemia ◽  
Human T Cell

AbstractOncogenic transformation of CD4+ T cells by human T-cell lymphotropic virus type 1 (HTLV-1) is understood as the initial step to adult T-cell leukemia/lymphoma, a process that is mainly initiated by perturbation of cellular signaling by the viral Tax oncoprotein, a potent transcriptional regulator. In search of novel biomarkers with relevance to oncogenesis, we identified the tumor marker and actin-bundling protein Fascin (FSCN1) to be specifically and strongly up-regulated in both HTLV-1–transformed and adult T-cell leukemia/lymphoma patient-derived CD4+ T cells. Fascin is important for migration and metastasis in various types of cancer. Here we report that a direct link can exist between a single viral oncoprotein and Fascin expression, as the viral oncoprotein Tax was sufficient to induce high levels of Fascin. Nuclear factor-κB signals were important for Tax-mediated transcriptional regulation of Fascin in T cells. This suggests that Fascin up-regulation by Tax contributes to the development of HTLV-1–associated pathogenesis.

scholarly journals Adult T-cell leukemia/lymphoma: report of two cases

2008 ◽  
Vol 41 (3) ◽  
pp. 288-292 ◽  
Author(s):  
Ricardo Aparecido Olivo ◽  
Fabrício Frederico Mendes Martins ◽  
Sheila Soares ◽  
Helio Moraes-Souza
Keyword(s):  
T Cell ◽  
Clinical Laboratory ◽  
Skin Lesions ◽  
Type I ◽  
T Cell Leukemia ◽  
Cell Leukemia ◽  
Laboratory Findings ◽  
Adult T Cell Leukemia ◽  
Human T Cell ◽  
Disease Case

Adult T-cell leukemia/lymphoma is a lymphoproliferative disorder of mature T lymphocytes associated with infection with human T-cell lymphotrophic virus type I (HTLV-I). Adult T-cell leukemia/lymphoma is characterized by clinical and laboratory polymorphism that allows it to be classified into four distinct subgroups: smoldering, chronic, acute and lymphomatous types. We present here two cases of adult T-cell leukemia/lymphoma, respectively in the acute and lymphomatous forms of the disease. Case 1 was a 35-year-old woman who presented abdominal distension accompanied by hepatosplenomegaly, adenomegaly, skin lesions, positivity for anti-HTLV-I antibodies and leukocytosis with the presence of flower cells. Case 2 was a 38-year-old man who was admitted with generalized lymphadenomegaly, positivity for anti-HTLV-I antibodies, hypercalcemia and osteolytic lesions. In this paper, we correlate the clinical-laboratory findings of these two cases with data in the literature.

scholarly journals Adult T-cell leukemia/lymphoma not associated with human T-cell leukemia virus type I.

1986 ◽  
Vol 83 (12) ◽  
pp. 4524-4528 ◽  
Author(s):  
M. Shimoyama ◽  
Y. Kagami ◽  
K. Shimotohno ◽  
M. Miwa ◽  
K. Minato ◽  
...  
Keyword(s):  
T Cell ◽  
Virus Type ◽  
Leukemia Virus ◽  
Type I ◽  
T Cell Leukemia ◽  
Cell Leukemia ◽  
Cell Leukemia Virus Type ◽  
Adult T Cell Leukemia ◽  
Human T Cell ◽  
T Cell Leukemia Virus
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