scholarly journals Global expression of noncoding RNome reveals dysregulation of small RNAs in patients with HTLV-1–associated adult T-cell leukemia: a pilot study

2020 ◽  
Author(s):  
Andrezza Nacimento ◽  
Daniela Raguer Valadão de Souza ◽  
Rodrigo Pessôa ◽  
Anna Julia Pietrobon ◽  
Youko Nukui ◽  
...  
Keyword(s):  
T Cell ◽  
Small Rnas ◽  
Mononuclear Cells ◽  
Illumina Miseq ◽  
Mapk Signaling ◽  
Peripheral Blood Mononuclear ◽  
Potential Implication ◽  
Adult T Cell Leukemia ◽  
Human T Cell ◽  
Pathway Analyses

Abstract Background Adult T cell lymphoma/leukemia (ATLL) is a peripheral T-cell neoplasm caused by human T-cell lymphotropic virus-1 (HTLV-1). Small RNAs (sRNAs), including microRNAs (miRNAs), play a pivotal role in the initiation and development of hematological malignancies and may represent potential therapeutic target molecules. However, little is known about how these molecules impact on the pathogenesis of ATLL. In this study, we aimed to identify sRNA expression signatures associated with ATLL and to investigate their potential implication in the pathophysiology of the disease. Methods Small-RNAseq analysis was performed in peripheral blood mononuclear cells from HTLV-1- associated ATLL (n = 10) in comparison to asymptomatic carriers (n = 8) and healthy controls (n = 5). Sequencing was carried out using the Illumina MiSeq platform, and the deregulation of selected miRNAs was validated by real-time PCR. Pathway analyses of most deregulated miRNA were performed and their global profiling was combined with transcriptome data in ATLL. Results The sequencing identified specific sRNAs signatures associated with ATLL patients that target pathways relevant in ATLL, such as TGF-β, Wnt, p53, apoptosis, and MAPK signaling cascades. Network analysis revealed several miRNAs regulating highly connected genes within the ATLL transcriptome. miR-451-3p was the most downregulated miRNA in active patients. Conclusions Our findings shed light on the expression of specific sRNAs in HTLV-1 associated ATLL, which may represent promising candidates as biomarkers that help monitor the disease activity.

scholarly journals Global expression of noncoding RNome reveals dysregulation of small RNAs in patients with HTLV-1–associated adult T-cell leukemia: a pilot study

2021 ◽  
Vol 16 (1) ◽  
Author(s):  
Andrezza Nascimento ◽  
Daniela Raguer Valadão de Souza ◽  
Rodrigo Pessôa ◽  
Anna Julia Pietrobon ◽  
Youko Nukui ◽  
...  
Keyword(s):  
T Cell ◽  
Small Rnas ◽  
Mononuclear Cells ◽  
Transforming Growth Factor ◽  
Illumina Miseq ◽  
Mapk Signaling ◽  
Mitogen Activated Protein Kinase ◽  
Peripheral Blood Mononuclear ◽  
Potential Implication ◽  
Human T Cell

Abstract Background Adult T cell lymphoma/leukemia (ATLL) is a peripheral T-cell neoplasm caused by human T-cell lymphotropic virus-1 (HTLV-1). Small RNAs (sRNAs), including microRNAs (miRNAs), play a pivotal role in the initiation and development of hematological malignancies and may represent potential therapeutic target molecules. However, little is known about how these molecules impact the pathogenesis of ATLL. In this study, we aimed to identify sRNA expression signatures associated with ATLL and to investigate their potential implication in the pathophysiology of the disease. Methods Small-RNAseq analysis was performed in peripheral blood mononuclear cells from HTLV-1- associated ATLL (n = 10) in comparison to asymptomatic carriers (n = 8) and healthy controls (n = 5). Sequencing was carried out using the Illumina MiSeq platform, and the deregulation of selected miRNAs was validated by real-time PCR. Pathway analyses of most deregulated miRNA were performed and their global profiling was combined with transcriptome data in ATLL. Results The sequencing identified specific sRNAs signatures associated with ATLL patients that target pathways relevant in ATLL, such as the transforming growth factor-(βTGF-β), Wnt, p53, apoptosis, and mitogen-activated protein kinase (MAPK) signaling cascades. Network analysis revealed several miRNAs regulating highly connected genes within the ATLL transcriptome. miR-451-3p was the most downregulated miRNA in active patients. Conclusions Our findings shed light on the expression of specific sRNAs in HTLV-1 associated ATLL, which may represent promising candidates as biomarkers that help monitor the disease activity.

scholarly journals Global expression of noncoding RNome reveals dysregulation of small RNAs in patients with HTLV-1–associated adult T-cell leukemia: a pilot study

2021 ◽  
Author(s):  
Andrezza Nacimento ◽  
Daniela Raguer Valadão de Souza ◽  
Rodrigo Pessôa ◽  
Anna Julia Pietrobon ◽  
Youko Nukui ◽  
...  
Keyword(s):  
T Cell ◽  
Small Rnas ◽  
Mononuclear Cells ◽  
Transforming Growth Factor ◽  
Illumina Miseq ◽  
Mapk Signaling ◽  
Mitogen Activated Protein Kinase ◽  
Peripheral Blood Mononuclear ◽  
Potential Implication ◽  
Human T Cell

Abstract Background: Adult T cell lymphoma/leukemia (ATLL) is a peripheral T-cell neoplasm caused by human T-cell lymphotropic virus-1 (HTLV-1). Small RNAs (sRNAs), including microRNAs (miRNAs), play a pivotal role in the initiation and development of hematological malignancies and may represent potential therapeutic target molecules. However, little is known about how these molecules impact the pathogenesis of ATLL. In this study, we aimed to identify sRNA expression signatures associated with ATLL and to investigate their potential implication in the pathophysiology of the disease. Methods: Small-RNAseq analysis was performed in peripheral blood mononuclear cells from HTLV-1- associated ATLL (n = 10) in comparison to asymptomatic carriers (n = 8) and healthy controls (n = 5). Sequencing was carried out using the Illumina MiSeq platform, and the deregulation of selected miRNAs was validated by real-time PCR. Pathway analyses of most deregulated miRNA were performed and their global profiling was combined with transcriptome data in ATLL. Results: The sequencing identified specific sRNAs signatures associated with ATLL patients that target pathways relevant in ATLL, such as the transforming growth factor-(βTGF-β), Wnt, p53, apoptosis, and mitogen-activated protein kinase (MAPK) signaling cascades. Network analysis revealed several miRNAs regulating highly connected genes within the ATLL transcriptome. miR-451-3p was the most downregulated miRNA in active patients. Conclusions: Our findings shed light on the expression of specific sRNAs in HTLV-1 associated ATLL, which may represent promising candidates as biomarkers that help monitor the disease activity.

scholarly journals The detection of human T cell leukemia virus proviral DNA and its application for classification and diagnosis of T cell malignancy

Blood ◽  
1984 ◽  
Vol 63 (5) ◽  
pp. 1235-1240 ◽  
Author(s):  
K Yamaguchi ◽  
M Seiki ◽  
M Yoshida ◽  
H Nishimura ◽  
F Kawano ◽  
...  
Keyword(s):  
T Cell ◽  
Mononuclear Cells ◽  
Leukemia Virus ◽  
T Cell Leukemia ◽  
Cell Leukemia ◽  
Peripheral Blood Mononuclear ◽  
Proviral Dna ◽  
Adult T Cell Leukemia ◽  
Human T Cell ◽  
T Cell Leukemia Virus

Abstract Adult T cell leukemia virus (HTLV or ATLV) proviral DNA integrated in the cellular DNA was examined by a modified Southern blotting method in the peripheral blood mononuclear cells and/or lymph node cells from 61 patients with adult T cell leukemia (ATL) and other hematologic diseases. Serum antibodies against ATL-associated antigens (ATLA) were also examined. The presence of human T cell leukemia virus (HTLV) proviral DNA was confirmed in all 20 patients with overt ATL and in 3 patients with T cell malignant lymphoma, who were seropositive but did not show clinical features characteristic of prototypic ATL. However, it was not detected in 6 antibody-positive healthy individuals and 8 seropositive patients with various hematologic disorders. Thus, the detection of proviral DNA by the method described here seems to be useful for the diagnosis of ATL in the endemic area and may provide a powerful tool for the classification of T cell malignancies.

scholarly journals Transmission of Human T-Cell Lymphotropic Virus Type 1 Tax to Rabbits by tax-Only-Positive Human Cells

2000 ◽  
Vol 7 (2) ◽  
pp. 274-278 ◽  
Author(s):  
Dorothea Zucker-Franklin ◽  
Bette A. Pancake ◽  
Parviz Lalezari ◽  
Manoochehr Khorshidi
Keyword(s):  
T Cell ◽  
Virus Type ◽  
Blood Donors ◽  
Mononuclear Cells ◽  
Spastic Paraparesis ◽  
The United States ◽  
Peripheral Blood Mononuclear ◽  
Adult T Cell Leukemia ◽  
Human T Cell

ABSTRACT The human T-cell lymphrotropic virus type 1 (HTLV-1) is causally related to adult T-cell leukemia and lymphoma and the neurodegenerative diseases tropical spastic paraparesis and HTLV-1-associated myelopathy. In the United States the prevalence of infection has been estimated to range from 0.016 to 0.1% on the basis of serologic tests for antibodies to the viral structural proteins. Blood from donors positive for antibodies to HTLV-1 or HTLV-2 is not used for transfusion. However, patients with the cutaneous T-cell lymphoma mycosis fungoides (MF) are HTLV-1 and -2 seronegative yet harbor proviral sequences identical to those that encode the HTLV-1 transactivating and transforming gene product p40tax in their peripheral blood mononuclear cells (PBMCs), and they usually have antibodies to p40 tax . Moreover, a study of 250 randomly selected blood donors revealed that approximately 8% of these seronegative individuals also had HTLV-1 tax sequences and antibodies to p40 tax , while they lacked sequences and antibodies related to gag, pol, or env. Thus, it seemed important to determine whether the “tax-only” state can be transmitted by transfusion. To this end, PBMCs from HTLV-1 and -2 seronegativetax-only-positive MF patients or from healthytax-only-positive blood donors were injected into adult rabbits, an established animal model for HTLV-1 infection. The PBMCs of all injected rabbits became tax sequence positive. These observations suggest that HTLV-1 tax can be transmitted bytax-only-positive mononuclear cells.

scholarly journals The detection of human T cell leukemia virus proviral DNA and its application for classification and diagnosis of T cell malignancy

Blood ◽  
1984 ◽  
Vol 63 (5) ◽  
pp. 1235-1240 ◽  
Author(s):  
K Yamaguchi ◽  
M Seiki ◽  
M Yoshida ◽  
H Nishimura ◽  
F Kawano ◽  
...  
Keyword(s):  
T Cell ◽  
Mononuclear Cells ◽  
Leukemia Virus ◽  
T Cell Leukemia ◽  
Cell Leukemia ◽  
Peripheral Blood Mononuclear ◽  
Proviral Dna ◽  
Adult T Cell Leukemia ◽  
Human T Cell ◽  
T Cell Leukemia Virus

Adult T cell leukemia virus (HTLV or ATLV) proviral DNA integrated in the cellular DNA was examined by a modified Southern blotting method in the peripheral blood mononuclear cells and/or lymph node cells from 61 patients with adult T cell leukemia (ATL) and other hematologic diseases. Serum antibodies against ATL-associated antigens (ATLA) were also examined. The presence of human T cell leukemia virus (HTLV) proviral DNA was confirmed in all 20 patients with overt ATL and in 3 patients with T cell malignant lymphoma, who were seropositive but did not show clinical features characteristic of prototypic ATL. However, it was not detected in 6 antibody-positive healthy individuals and 8 seropositive patients with various hematologic disorders. Thus, the detection of proviral DNA by the method described here seems to be useful for the diagnosis of ATL in the endemic area and may provide a powerful tool for the classification of T cell malignancies.

scholarly journals Transcriptomic Profiling of Tumor-Infiltrating CD4+TIM-3+ T Cells Reveals Their Suppressive, Exhausted, and Metastatic Characteristics in Colorectal Cancer Patients

Vaccines ◽  
2020 ◽  
Vol 8 (1) ◽  
pp. 71 ◽  
Author(s):  
Varun Sasidharan Nair ◽  
Salman M Toor ◽  
Rowaida Z Taha ◽  
Ayman A Ahmed ◽  
Mohamed A Kurer ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
T Cells ◽  
T Cell ◽  
Mononuclear Cells ◽  
T Regulatory Cell ◽  
Peripheral Blood Mononuclear ◽  
Functional Studies ◽  
Normal Tissues ◽  
Pathway Analyses ◽  
Colorectal Cancer Patients

T cell immunoglobulin mucin-3 (TIM-3) is an immune checkpoint identified as one of the key players in regulating T-cell responses. Studies have shown that TIM-3 is upregulated in the tumor microenvironment (TME). However, the precise role of TIM-3 in colorectal cancer (CRC) TME is yet to be elucidated. We performed phenotypic and molecular characterization of TIM-3+ T cells in the TME and circulation of CRC patients by analyzing tumor tissues (TT, TILs), normal tissues (NT, NILs), and peripheral blood mononuclear cells (PBMC). TIM-3 was upregulated on both CD4+ and CD3+CD4− (CD8+) TILs. CD4+TIM-3+ TILs expressed higher levels of T regulatory cell (Tregs)-signature genes, including FoxP3 and Helios, compared with their TIM-3− counterparts. Transcriptomic and ingenuity pathway analyses showed that TIM-3 potentially activates inflammatory and tumor metastatic pathways. Moreover, NF-κB-mediated transcription factors were upregulated in CD4+TIM-3+ TILs, which could favor proliferation/invasion and induce inflammatory and T-cell exhaustion pathways. In addition, we found that CD4+TIM-3+ TILs potentially support tumor invasion and metastasis, compared with conventional CD4+CD25+ Tregs in the CRC TME. However, functional studies are warranted to support these findings. In conclusion, this study discloses some of the functional pathways of TIM-3+ TILs, which could improve their targeting in more specific therapeutic approaches in CRC patients.

scholarly journals Antigenic Equivalence of Human T-Cell Responses toMycobacterium tuberculosis-Specific RD1-Encoded Protein Antigens ESAT-6 and Culture Filtrate Protein 10 and to Mixtures of Synthetic Peptides

2000 ◽  
Vol 68 (6) ◽  
pp. 3314-3321 ◽  
Author(s):  
Sandra M. Arend ◽  
Annemieke Geluk ◽  
Krista E. van Meijgaarden ◽  
Jaap T. van Dissel ◽  
Michael Theisen ◽  
...  
Keyword(s):  
T Cell ◽  
Culture Filtrate ◽  
Large Scale ◽  
Mononuclear Cells ◽  
Genomic Region ◽  
Protein Antigens ◽  
Peripheral Blood Mononuclear ◽  
Human T Cell ◽  
Peptide Mixtures ◽  
Culture Filtrate Protein

ABSTRACT The early secreted antigenic target 6-kDa protein (ESAT-6) and culture filtrate protein 10 (CFP-10) are promising antigens for reliable immunodiagnosis of tuberculosis. Both antigens are encoded by RD1, a genomic region present in all strains of Mycobacterium tuberculosis and M. bovis but lacking in all M. bovis bacillus Calmette-Guérin vaccine strains. Production and purification of recombinant antigens are laborious and costly, precluding rapid and large-scale testing. Aiming to develop alternative diagnostic reagents, we have investigated whether recombinant ESAT-6 (rESAT-6) and recombinant CFP-10 (rCFP-10) can be replaced with corresponding mixtures of overlapping peptides spanning the complete amino acid sequence of each antigen. Proliferation of M. tuberculosis-specific human T-cell lines in response to rESAT-6 and rCFP-10 and that in response to the corresponding peptide mixtures were almost completely correlated (r = 0.96,P < 0.0001 for ESAT-6; r = 0.98,P < 0.0001 for CFP-10). More importantly, the same was found when gamma interferon production by peripheral blood mononuclear cells in response to these stimuli was analyzed (r = 0.89, P < 0.0001 for ESAT-6;r = 0.89, P < 0.0001 for CFP-10). Whole protein antigens and the peptide mixtures resulted in identical sensitivity and specificity for detection of infection with M. tuberculosis. The peptides in each mixture contributing to the overall response varied between individuals with different HLA-DR types. Interestingly, responses to CFP-10 were significantly higher in the presence of HLA-DR15, which is the major subtype of DR2. These results show that mixtures of synthetic overlapping peptides have potency equivalent to that of whole ESAT-6 and CFP-10 for sensitive and specific detection of infection with M. tuberculosis, and peptides have the advantage of faster production at lower cost.

scholarly journals Effect of Lamivudine on Transmission of Human T-Cell Lymphotropic Virus Type 1 to Adult Peripheral Blood Mononuclear Cells In Vitro

2002 ◽  
Vol 46 (9) ◽  
pp. 3080-3083 ◽  
Author(s):  
Emanuela Balestrieri ◽  
Giancarlo Forte ◽  
Claudia Matteucci ◽  
Antonio Mastino ◽  
Beatrice Macchi
Keyword(s):  
T Cell ◽  
Virus Type ◽  
Peripheral Blood Mononuclear Cells ◽  
Peripheral Blood ◽  
Mononuclear Cells ◽  
Peripheral Blood Mononuclear ◽  
Human T Cell ◽  
Blood Mononuclear Cells

ABSTRACT The effects of lamivudine (3TC) on in vitro infection of peripheral blood mononuclear cells (PBMC) from healthy donors with human T-cell lymphotropic virus type 1 (HTLV-1) were investigated. Direct measures of viral replication (viral DNA, RNA, and protein) all gave similar, very high 50% inhibitory concentrations in comparison with those previously reported for zidovudine. Nevertheless, 3TC inhibited HTLV-1-driven long-term growth of infected PBMC in vitro at concentrations (6.25 μM) which had poor or no direct antiviral effects, suggesting that another mechanism may be playing a role.

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