A new study published in Blood found that a new ultra-sensitive test can detect the D816V KIT gene mutation, a common sign of systemic mastocytosis (SM) and other mast cell disorders, in patients who previously tested negative for the mutation.
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.
“KIT p.D816V may be undetected due to a low mutated cell burden in blood and bone marrow (BM) of many patients, particularly among those without skin lesions,” the authors said, highlighting the need for improved tests for these individuals.
The Flow-SuperRCA assay is a new, advanced test that can detect the D816V mutation in both the blood and bone marrow, even in patients who have very few cells with the mutation. Here, the authors compared the Flow-SuperRCA test to the more commonly used ASOqPCR test.
Read more about SM testing and diagnosis
The study included 337 adults with mast cell activation syndrome (MCAS) and 220 patients with mastocytosis, including several subtypes of SM. All patients gave a bone marrow sample, blood sample or both.
With the more commonly used ASOqPCR test, findings revealed that 83% of patients with SM tested positive for the mutation in their bone marrow, with 55% also testing positive in their blood. An additional 15% of patients were found to have the mutation after the sample was purified. The mutation could not be detected in 2% of individuals with SM.
Among all participants, Flow-SuperRCA resulted in significantly higher D186V mutation positivity rates. “Globally, these results translated in a greater accuracy of 94% vs 87% in BM and of 86% vs 76% in PB [peripheral blood], for the Flow-SuperRCA vs ASOqPCR assays, respectively,” the authors wrote.
In the patients with SM, 97.5% tested positive for the D816V KIT mutation using Flow-SuperRCA. Participants with bone marrow mastocytosis (BMM), a subtype of SM, saw the biggest improvement in positivity rate using Flow-SuperRCA. Four patients were not found to have the mutation, the same finding as with ASOqPCR.
The authors cautioned that barriers remain before the use of Flow-SuperRCA can become widespread, including availability, cost and time to prepare samples.
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