A new study has compared KIT D816V mutational status in blood versus bone marrow samples to screen for systemic mastocytosis (SM) and other mast cell activation syndromes (MCAS) and found it has high specificity but limited sensitivity in blood.

The study, published in Allergy, also assessed the follow-up kinetics of the KIT D816V and associated outcomes.

“The availability of high-sensitive real-time allele-specific oligonucleotide-qPCR (ASO-qualitative polymerase chain reaction) and digital PCR methods has demonstrated the KIT D816V mutation in blood of the majority of SM patients, including advanced forms of SM (AdvSM), indolent SM [ISM], and to a lesser extent [bone marrow] mastocytosis [BMM] patients,” the authors wrote. “However, few studies have investigated the KIT D816V mutation in paired [bone marrow] and blood samples from large series of children and adults diagnosed with mastocytosis.”

The research team employed a high-sensitive molecular technique to assess the burden of KIT D816V mutation in paired, EDTA-anticoagulated bone marrow and blood samples and also in gDNA from bone marrow mast cells from 368 patients diagnosed with MCAS and mastocytosis in the skin. The patients were recruited from 2 centers in Spain between July 2008 and July 2021.

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Despite a high correlation between KIT D816V status in blood and bone marrow, a significant portion of the cases who tested negative by ASO-qualitative PCR for KIT D816V in whole blood and whole bone marrow gDNA were in fact found to harbor the mutation in purified bone marrow mast cells. These results suggest that KIT D816V might go undetected in whole blood gDNA by ASO-qualitative PCR. Further purification of distinct myeloid cell populations revealed that two-thirds of those who tested negative harbored the mutation in eosinophils and basophils.

The authors suspect the reason for the initial negative results might be the relatively lower burden of KIT D816V-mutated cells in the blood of these patients. The team recommends an ultrasensitive approach to the analysis by using purified blood eosinophils and/or basophils, which will lead to earlier and more accurate diagnoses of clonal mast cell diseases via blood analysis, a less invasive approach than previously has been required.

Reference

Navarro-Navarro P, Alvarez-Twose I, Pérez-Pons A, et al. KITD816V mutation in blood for the diagnostic screening of systemic mastocytosis and mast cell activation syndromes. Allergy. Published online November 16, 2022. doi:10.1111/all.15584