A recent study found that including baseline serum tryptase (BST) levels, KIT mutation testing and TPSAB1 mutation analysis in the workup for systemic mastocytosis (SM) can significantly improve diagnosis. Results will be presented at the upcoming American Society of Hematology Annual Meeting and Exposition.
What is a KIT gene mutation?
SM is usually caused by a sporadic mutation in the KIT gene, which codes for a protein called CD117 transmembrane tyrosine kinase. The protein is involved in the growth, survival and migration of mast cells. The most common KIT mutation associated with SM is the D816V mutation, which results in the amino acid aspartic acid being replaced by the amino acid valine in the protein chain.
One of the diagnostic criteria for SM is a BST level of at least 20 µg/L. However, individuals with hereditary alpha-tryptasemia, a disease caused by TPSAB1 mutations, can also have elevated BST levels. To further complicate matters, many symptoms of SM and hereditary alpha-tryptasemia overlap, which can lead to unnecessary testing and misdiagnosis.
To develop their diagnostic tool, the authors analyzed blood samples from 228 patients with SM. This allowed them to identify biomarker thresholds that may be predictive of the disease.
Read more about SM testing and diagnosis
Next, the investigators tested their model in a sample of 142 individuals from several hematology departments in Germany. The model recommended bone marrow biopsies for SM in patients without TPSAB1 mutations who have BST levels above 15 µg/L.
If participants also tested positive for the KIT D816V mutation, the model recommended bone marrow biopsies if their BST levels fell between 11.5 and 14.9 µg/L.
Notably, the algorithm identified 41 cases of SM that would have been missed using BST levels alone. Additionally, the model ruled out SM for 17 patients with BST levels of 20 µg/L or greater who may have undergone unnecessary testing otherwise.
The authors calculated that 88% of individuals who truly had SM tested positive through their algorithm. Conversely, only 26% of individuals with the disease tested positive using the BST criterion alone.
Together, these findings highlight the potential of combining blood testing with genetic analysis to differentiate between these two conditions.
“This non-invasive approach optimizes patient selection for invasive diagnostics and may serve as a new standard for early and accurate SM screening,” the authors concluded.
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