Kaposiform lymphangiomatosis effectively treated with MEK inhibition
Jessica B Foster1, Dong Li2, Michael E March2
1Division of Oncology, Children's Hospital of Philadelphia, Philadelphia, PA, USA.
Abstract:
Kaposiform lymphangiomatosis (KLA) is a rare lymphatic anomaly primarily affecting the mediastinum with high mortality rate. We present a patient with KLA and significant disease burden harboring a somatic point mutation in the Casitas B lineage lymphoma (CBL) gene. She was treated with MEK inhibition with complete resolution of symptoms, near-complete resolution of lymphatic fluid burden, and remodeling of her lymphatic system. While patients with KLA have been reported to harbor mutations in NRAS, here we report for the first time a causative mutation in the CBL gene in a patient with KLA, successfully treated with Ras pathway inhibition.
Insights
Kaposiform lymphangiomatosis (KLA) is a rare condition. A patient with KLA and a CBL gene mutation was successfully treated with MEK inhibition, showing complete symptom resolution and lymphatic system remodeling.
Area of Science:
- Vascular anomalies
- Genetics
- Oncology
Background:
- Kaposiform lymphangiomatosis (KLA) is a rare, aggressive lymphatic vascular anomaly.
- It primarily affects the mediastinum and carries a high mortality rate.
- Previous research identified NRAS mutations in KLA patients.
Observation:
- A KLA patient presented with significant disease burden.
- Genetic analysis revealed a somatic point mutation in the Casitas B lineage lymphoma (CBL) gene.
- This is the first report of a CBL gene mutation in KLA.
Findings:
- The patient was treated with MEK inhibition, targeting the Ras pathway.
- Treatment resulted in complete resolution of symptoms.
- Near-complete resolution of lymphatic fluid burden and lymphatic system remodeling were observed.
Implications:
- This study identifies CBL gene mutations as a potential driver in KLA.
- MEK inhibition demonstrates therapeutic efficacy in KLA with CBL mutations.
- This offers a novel therapeutic strategy for KLA patients with specific genetic alterations.
