The aim of this study is to analyze available research on targeting signaling pathways for the development of new drugs in patients with T-cell acute lymphoblastic leukemia (T-ALL). This analysis focuses specifically on the role of LCK tyrosine kinase and mTOR signaling pathways in pediatric patients. Outcome: Current literature suggests that these pathways play a significant role in the regulation of T-cell cycles, making them potential therapeutic targets. However, despite promising findings, there remains a need for further research, particularly in pediatric populations, to fully understand the therapeutic implications and to optimize drug development. The conclusion drawn from this analysis highlights the significant influence of LCK and mTOR on T-cell cycle regulation, underscoring the importance of continued investigation in this area.
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http://dx.doi.org/10.2147/TACG.S494389 | DOI Listing |
Immunol Rev
January 2025
Signaling Research Centers BIOSS and CIBSS, University of Freiburg, Freiburg, Germany.
Rather than being contained in a single polypeptide, and unlike receptor tyrosine kinases, the T cell receptor (TCR) divides its signaling functions among its subunits: TCRα/β bind the extracellular ligand, an antigenic peptide-MHC complex (pMHC), and the CD3 subunits (CD3γ, CD3δ, CD3ε, and CD3ζ) transmit this information to the cytoplasm. How information about the quality of pMHC binding outside is transmitted to the cytoplasm remains a matter of debate. In this review, we compile data generated using a wide variety of experimental systems indicating that TCR engagement by an appropriate pMHC triggers allosteric changes transmitted from the ligand-binding loops in the TCRα and TCRβ subunits to the cytoplasmic tails of the CD3 subunits.
View Article and Find Full Text PDFEur J Med Chem
February 2025
Borch Department of Medicinal Chemistry and Molecular Pharmacology, Purdue University, West Lafayette, IN 47907, USA; James Tarpo Jr. and Margaret Tarpo Department of Chemistry, Purdue University, West Lafayette, IN 47907, USA; Institute for Drug Discovery, Purdue University, West Lafayette, IN 47907, USA; Institute for Cancer Research, Purdue University, West Lafayette, IN 47907, USA. Electronic address:
Protein tyrosine phosphatase non-receptor type 22 (PTPN22) lies downstream of the T cell receptor (TCR) and attenuates T cell signaling by dephosphorylating key effector proteins such as LCK, Zap70, and the intracellular region of the TCR. Recent evidence implicates PTPN22 as an exciting target for enabling immunotherapeutic efficacy against cancer. We carried out structural optimization of a benzofuran salicylic acid-based orthosteric PTPN22 inhibitor 8b, using a combination of crystal structure analysis, synthesis, matched molecular pairs analysis, and biochemical and cell-based assays.
View Article and Find Full Text PDFCell Mol Immunol
December 2024
The Key Laboratory for Human Disease Gene Study of Sichuan Province and the Department of Laboratory Medicine, Sichuan Provincial People's Hospital, University of Electronic Science and Technology of China, Chengdu, China.
Biochem Pharmacol
December 2024
Department of Pharmacology, School of Medicine, Daegu Catholic University, 33 Duryugongwon-ro 17-gil, Nam-gu, Daegu 42472, Republic of Korea. Electronic address:
Isobavachin, isolated from Psoralea corylifolia L. exhibits therapeutic potential for osteoporosis or skin disease. Here, we evaluated the pharmacological effects of isobavachin on IgE-dependent inflammatory allergic reactions, as well as the underlying mechanisms, in bone marrow-derived mast cells and a mouse model of passive cutaneous anaphylaxis (PCA).
View Article and Find Full Text PDFNeoplasia
January 2025
Department of Life Sciences, Korea University, Seoul 02841, Republic of Korea. Electronic address:
X-linked inhibitor of apoptosis-associated factor 1 (XAF1) is a stress-inducible tumor suppressor that is commonly inactivated in multiple types of human malignancies. Nevertheless, the molecular basis for the XAF1-mediated tumor suppression remains largely undefined. Here, we report that XAF1 is secreted from cells under various cytotoxic stress conditions and activates T cell-mediated tumor surveillance.
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