Researchers from the University of Tsukuba show that angioimmunoblastic T-cell lymphoma (AITL) is dependent on T-cell receptor (TCR) signaling and that dasatinib, a multi-kinase inhibitor that targets the TCR pathway, may improve treatment outcomes.
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‘Angioimmunoblastic T-cell lymphoma is highly dependent on TCR signaling and dasatinib holds potential to treat it.’
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Lymphomas form a group of related cancers that affect the lymphatic system. They are classified according to the type of white blood cells (lymphocytes) affected as B-cell lymphomas or T-cell lymphomas.Read More..
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AITL is a rare and often aggressive T-cell lymphoma with a five-year survival of below 30%. Patients with AITL present with high fever, skin rash, and symptoms suggestive of immune activation.
Many patients have specific altered genes including the DNMT3A, TET2, IDH2, and RhoA genes, though the exact role these gene mutations play in the development of the disease is not fully understood.
Researchers at the University of Tsukuba first showed that TET2 loss paired with expression of the G17V RHoA mutant in mice led to development of AITL-like lymphoma. By targeting the TCR pathway, dasatinib successfully suppressed disease progression in AITL model mice and prolonged survival.
"Our findings suggest that AITL is highly dependent on TCR signaling and that dasatinib could be a promising candidate drug for AITL treatment," says Dr Mamiko Sakata-Yanagimoto, Associate Professor at the department of Hematology, Faculty of Medicine, and a senior author of the study.
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"Recently, many new drugs have been introduced as promising therapeutics for Primary T-Cell Lymphomas including AITL," says Professor Shigeru Chiba, main author of the study.
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Dasatinib, an oral drug long used to treat specific Philadelphia chromosome-positive leukemias, is on the WHO Model List of Essential Medicines. Given the encouraging outcomes of this study, further research is needed to firmly establish its place amongst therapeutics for AITL, especially regarding efficacy against specific mutations as well as clinical applicability and safety profile.
Source-Eurekalert