Adult T cell leukemia (ATL) is an aggressive blood malignancy secondary to chronic infection with the human T cell leukemia virus type I (HTLV-1) retrovirus. ATL encompasses four subtypes (acute, lymphoma, chronic, and smoldering), which exhibit different clinical characteristics and respond differently to various treatment strategies. Yet, all four subtypes are characterized by a dismal long-term prognosis and a low survival rate. While antiretroviral therapy improves overall survival outcomes in smoldering and chronic subtypes, survival remains poor in lymphoma subtypes despite their good response to intensive chemotherapy. Nonetheless, acute ATL remains the most aggressive form associated with profound immunosuppression, chemo-resistance and dismal prognosis. Targeted therapies such as monoclonal antibodies, epigenetic therapies, and arsenic/IFN, emerged as promising therapeutic approaches in ATL. Allogeneic hematopoietic cell transplantation is the only potentially curative modality, alas applicable to only a small percentage of patients. The recent findings demonstrating the expression of the viral oncoprotein Tax in primary ATL cells from patients with acute or chronic ATL, albeit at low levels, and their dependence on continuous Tax expression for their survival, position ATL as a virus-addicted leukemia and validates the rationale of anti-viral treatment strategies. This review provides a comprehensive overview on conventional, anti-viral and targeted therapies of ATL, with emphasis on Tax-targeted therapied in the pre-clinical and clinical settings.
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http://dx.doi.org/10.1016/j.leukres.2024.107598 | DOI Listing |
Nat Prod Res
December 2024
State Key Laboratory of Food Nutrition and Safety, Key Laboratory of Industrial Fermentation Microbiology, College of Biotechnology, Tianjin University of Science and Technology, Tianjin, China.
T-cell acute lymphoblastic leukaemia (T-ALL) is a common childhood malignant tumour, which has poor prognosis and high recurrence rate. Ginsenoside Rh2 (GRh2), a bioactive ingredient of has significant anti-tumour effect. In this study, we found that gene expressions of Jurkat cells were significantly changed in the mitogen-activated protein kinase (MAPK) and phosphatidylinositol 3 kinase (PI3K)/protein kinase B (AKT) signalling pathways after 35 µm GRh2 treatment, involving in JUN, PIEN, AKT3 and MAPK8IP2.
View Article and Find Full Text PDFBiol Direct
December 2024
Department of Gynaecology and Obstetrics, Sichuan Provincial People's Hospital, University of Electronic Science and Technology of China, No. 32, West Second Section, 1st Ring Road, Qingyang District, Chengdu, 610072, Sichuan Province, China.
This study explores the epigenetic mechanism of MLL1 regulating trophoblast ferroptosis in preeclampsia (PE). A murine model of PE was established, and HTR-8/SVneo cells were induced by Erastin to establish an in vitro cell model. GSH, MDA, Fe, and ROS levels were measured to assess ferroptosis.
View Article and Find Full Text PDFCancer Lett
December 2024
Department of Biochemistry and Molecular Genetics, University of Illinois at Chicago, Chicago, USA; Enzyme by Design Inc., Chicago, USA; Research Biologist, Biological Science Research and Development, Department of Veterans Affairs Medical Center, Chicago, Illinois, USA. Electronic address:
L-asparaginase (L-ASNase) is crucial in treating pediatric acute lymphoblastic leukemia (ALL), but its use is hampered by side effects from the immunogenicity and L-glutaminase (L-GLNase) co-activity of FDA-approved bacterial L-ASNases, often leading to treatment discontinuation and poor outcomes. The toxicity of these L-ASNases makes them especially challenging to use in adult cancer patients. To overcome these issues, we developed EBD-200, a humanized guinea pig L-ASNase with low Km and no L-GLNase activity, eliminating glutamine-related toxicity.
View Article and Find Full Text PDFHum Pathol
December 2024
Department of Hematopathology, The University of Texas MD Anderson Cancer Center, Houston, Texas, USA. Electronic address:
Flow cytometry immunophenotypic analysis is an important and indispensable tool in the diagnosis of mature B-cell lymphomas/leukemias, particularly for small fine needle aspiration and needle core biopsy specimens which are becoming increasingly popular for diagnostic purposes. Flow cytometry immunophenotyping (FCI) has several advantages. Given its multiparametric nature, FCI can analyze the expression of multiple antigens simultaneously on the same cell of interest, qualitatively and quantitively.
View Article and Find Full Text PDFBiochem Pharmacol
December 2024
Department of Biochemistry and Molecular Biology, School of Basic Medical Sciences, Shenzhen University Medical School, Shenzhen University, Shenzhen 518055, China. Electronic address:
Activation of immunoglobulin E (IgE)-associated mast cells (MCs) triggers the onset of pro-inflammatory signals associated with type I allergic diseases. Although histone acetylation changes have been associated with inflammatory diseases, the impact of lysine-acetyltransferase (KAT) inhibitors on IgE-mediated MCs function is unclear. Potential anti-allergic effects of the KAT6A inhibitor WM-1119 on IgE-mediated MCs activation and allergic inflammation were examined in this study.
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