Abnormal lymph vessels show heightened growth signaling regardless of key gene mutation
Lymphatic malformations are rare disorders in which lymph vessels develop abnormally, often beginning in childhood and sometimes causing swelling, infection, bleeding, pain or airway obstruction.
Researchers from the University of Osaka have conducted an extensive study on lymphatic malformations, a rare disorder characterized by abnormal development of lymph vessels. Through genetic analysis and examination of tissue samples from 34 patients, they identified common features of the disease and potential molecular clues for future treatment strategies.
The PIK3CA gene, known to contribute to abnormal lymphatic vessel growth, was found in 58.8% of the patients analyzed. Interestingly, malformed vessels exhibited a more scattered growth pattern in patients carrying PIK3CA mutations, but clinical features were similar regardless of mutation presence. The PI3K/AKT/mTOR signaling pathway, a major cell-growth signaling system, was found to be more active in malformed lymphatic vessels, and AKT activity increased with patient age.
Spatial transcriptomic analysis revealed that ten genes were more active in malformed vessels, with NFATC1 being strongly expressed in the endothelial cells lining these vessels. This suggests that the calcineurin-NFAT pathway may also contribute to disease pathogenesis and could serve as a future therapeutic target. The researchers aim to refine existing treatments and guide the search for new ones based on this integrated view of lymphatic malformations from genetic changes to pathological morphology and molecular activity.
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