Blood
Department of Pathology and Laboratory Medicine, Center for Viral Oncology, University of Kansas Medical Center, Kansas City, KS.
Published: May 2016
Human T-cell leukemia virus type 1 (HTLV-1)-associated adult T-cell leukemia and T-cell lymphoma (ATL) are aggressive diseases with poor prognoses, limited therapeutic options, and no curative treatment. In this study, we used a mouse model of ATL and restored expression of the microRNA, miR-124a, to identify in vivo downstream effectors responsible for its tumor-suppressive functions in ATL cells. Our results revealed that STAT3, a direct target of miR-124a, is constitutively activated in HTLV-I-transformed cells and ATL cells, and activating STAT3 mutations were detected in 25.5% of primary ATL patients. Interestingly, we found that the STAT3 downstream kinase effector, Pim1, is constitutively activated in ATL cells. The dependence of ATL cells to Pim1 activity was demonstrated using 2 Pim1 small inhibitors, SMI-4a and AZD1208. These studies indicated that HTLV-I-transformed and ATL cells, but not normal peripheral blood mononuclear cells, are highly sensitive to AZD1208, and the inhibition of Pim1 signaling triggers an apoptotic signal in leukemic cells. Finally, preclinical testing of AZD1208 in a mouse model of ATL resulted in significant prevention of tumor growth in vivo. In conclusion, our studies suggest that constitutive activation of the STAT3-Pim1 pathway represents a novel therapeutic target for the treatment of ATL.
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http://dx.doi.org/10.1182/blood-2015-11-685032 | DOI Listing |
PLoS Comput Biol
January 2025
Department of Hematology, Rheumatology and Infectious Disease, Faculty of Life Sciences, Kumamoto University, Kumamoto, Japan.
Human T-cell leukemia virus type 1 (HTLV-1) causes adult T-cell leukemia (ATL) and HTLV-1-associated myelopathy (HAM) after a long latent period in a fraction of infected individuals. These HTLV-1-infected cells typically have phenotypes similar to that of CD4+T cells, but the cell status is not well understood. To extract the inherent information of HTLV-1-infected CD4+ cells, we integratively analyzed the ATAC-seq and RNA-seq data of the infected cells.
View Article and Find Full Text PDFInt J Hematol
December 2024
Department of Pathology, Imamura General Hospital, Kagoshima, Japan.
Here, we report a rare case of relapsed adult T-cell leukemia-lymphoma (ATL) with evidence of clonal relapse 26 years after initial diagnosis. The patient had been diagnosed with an aggressive form of lymphoma-type ATL 26 years prior and did not receive further ATL treatment for approximately 26 years after achieving complete remission. We used nested PCR to identify the amplification of ATL clone-specific accumulation sites in DNA from hematoxylin and eosin-stained specimens from the patient.
View Article and Find Full Text PDFInt Immunopharmacol
January 2025
Department of Cardiology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China; Hubei Key Laboratory of Biological Targeted Therapy, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, China; Hubei Engineering Research Center for Immunological Diagnosis and Therapy of Cardiovascular Diseases, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, China. Electronic address:
Background: Cardiac fibrosis, a critical factor in myocardial remodeling post-myocardial infarction (MI), can advance heart failure progression. Atractylenolide III (ATL-III), derived from Atractylodes lancea, has recognized antioxidant and anti-inflammatory effects; however, its influence on cardiac fibrosis remains unclear.
Methods: MI was induced in mice by permanent ligation of the left anterior descending (LAD) coronary artery, followed by 2 weeks of ATL-III or dimethyl sulfoxide (DMSO) treatment.
Expert Rev Hematol
December 2024
Department of Hematology, Osaka International Cancer Institute, Osaka, Japan.
Introduction: Spontaneous regression (SR) is observed in some patients with mature T-cell non-Hodgkin lymphoma (MTCL), including adult T-cell leukemia/lymphoma (ATL), although the incidence is rare.
Area Covered: We extracted 31 cases with MTCL who experienced SR based on a literature search and summarized the patient characteristics and clinical outcomes.
Expert Opinion: MTCL with SR included various subtypes, the most common being ATL ( = 17).
Leuk Res
December 2024
National Centre for Human Retrovirology and Department of Haematology, Imperial College Healthcare NHS Trust, UK; Department of Immunology & Inflammation, Imperial College London, UK. Electronic address:
Human T-cell leukaemia virus type-1 (HTLV-1) causes the highly aggressive malignancy adult T-cell leukaemia-lymphoma (ATL) in approximately 5 % of chronically infected carriers. HTLV-1 persists in the host by enhancing survival of infected-T-cells despite the presence of a strong immune response. Therefore, asymptomatic HTLV-1 carriers have a lifelong balance between infected cell proliferation and the host antiviral immune response.
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