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2023 CLA Conference

Cellular Mechanisms Underlying PIK3CA-driven Lymphatic Anomalies

Unraveling the Mysteries of Microcystic Lymphatic Malformations

Have you ever wondered about the intricate world of rare diseases and the groundbreaking research being conducted to understand and combat them? Today, let's dive into the realm of microcystic lymphatic malformations, a condition that affects the delicate lymphatic system in our bodies.

Imagine a network of tiny vessels, much like rivers, coursing through your body. These vessels make up the lymphatic system, responsible for maintaining fluid balance and supporting our immune system. However, in some cases, these intricate channels can go awry, leading to conditions like microcystic lymphatic malformations.

Researchers have delved deep into this mysterious world, using mouse models to uncover the underlying causes of these anomalies. One key player in the drama is the PIK3CA gene, responsible for encoding the catalytic subunit of the P85 kinase enzyme. When mutations occur within this gene, it triggers a cascade of events that result in the development of microcystic lymphatic malformations.

The researchers have meticulously studied these anomalies in two distinct forms: macrocystic lymphatic malformations with large fluid-filled cysts, often found in the head and neck region, and microcystic lymphatic malformations with small lymphatic channels that infiltrate deep into tissues.

What's particularly intriguing is the role of a unique population of cells marked by high levels of a protein called PTX3. These cells, located at the terminal ends of lymphatic capillaries, undergo hyperproliferation and migration due to the PIK3CA gene mutation. This sets off a domino effect involving the upregulation of genes associated with immune modulation and the recruitment of immune cells, specifically macrophages.

The immune cells, in turn, produce factors like VEGF-C, promoting the sustained growth of these malformations. Armed with this knowledge, researchers have explored potential therapeutic interventions. Inhibiting the paracrine signaling between these cells and immune cells has shown promise in limiting the expansion of microcystic lymphatic malformations.

Excitingly, recent research has expanded beyond embryonic models to explore microcystic lymphatic malformations in internal organs, offering new insights into their development and potential treatments.

This journey into the intricacies of microcystic lymphatic malformations highlights the dedication of scientists and the strides they are making in understanding, diagnosing, and potentially treating rare diseases. As we unravel the mysteries of our own biology, we inch closer to innovative solutions that could improve the lives of those affected by these conditions.