A full workup including blood testing and bone marrow biopsies can capture cases of systemic mastocytosis (SM) that may be missed from blood genetic detection alone, making them a valuable tool when mast cell disease is suspected, notes a study recently published in Clinical Lymphoma, Myeloma and Leukemia.
The KIT D816V mutation can be identified via blood testing or bone marrow biopsy. This mutation is very common in patients with clonal mast cell disease (cMCD), a group of disorders that includes SM. “However, some cMCD patients with low circulating KIT D816V may still evade detection via [peripheral blood] testing,” the authors wrote.
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.
In some of these individuals, the mutation is more readily detectable in the bone marrow, leading to missed diagnoses when the blood alone is used.
Read more about SM testing and diagnosis
Findings of this study were based on the PROSPECTOR study, which aimed to determine the prevalence of KIT D816V mutations in 381 patients with anaphylaxis or signs of systemic mast cell activation in at least two different organ systems.
The study included 27 individuals from the original PROSPECTOR study. All participants had elevated basal serum tryptase levels, no evidence of hereditary alpha-tryptasemia and variations in theTPSAB1 gene. According to the National Institutes of Health, individuals with these characteristics may have cMCD.
The authors found that 22 patients were diagnosed with cMCD through repeat KIT D816V testing (30%), bone marrow biopsy (7%) or both (63%). Notably, of the 22 patients diagnosed with cMCD, 64% initially tested negative for the KIT D816V mutation.
Based on these results, the authors suggest that patients with these clinical characteristics, especially those experiencing anaphylaxis and widespread mast cell activation, should receive a bone marrow biopsy to confirm a cMCD diagnosis.
Sign up here to get the latest news, perspectives, and information about SM sent directly to your inbox. Registration is free and only takes a minute.
