Different KIT mutations in patients with systemic mastocytosis (SM) appear to correlate with certain findings under the microscope. This discovery could help diagnose patients more accurately and allow for better treatment selection in each case, according to a recently published abstract in the Journal of Human Immunity.
Understanding SM and the KIT mutation
Over 90% of patients with SM have the KIT D816V mutation. This gene mutation causes uncontrolled activation of the KIT receptor, which in turn leads to excessive mast cell proliferation and activation.
Other forms of KIT mutations observed in SM include the D816Y and D816F variants, which affect different regions of the KIT gene.
Despite this knowledge, the way in which different KIT variants influence the course of the disease and its response to treatment is not yet fully understood.
Different KIT mutations look different under the microscope
The authors aimed to assess the microscopic characteristics (morphology) of different KIT mutations in the bone marrow.
The study included over 400 patients with a confirmed SM diagnosis according to World Health Organization (WHO) criteria. Over 95% of patients had either the D816V or D816Y mutation.
Patients with the D816V and D816Y mutations exhibited a particular mast cell morphology in the bone marrow, specifically spindled cells. Interestingly, the authors observed that seven out of 18 patients without the D816V or D816F mutations had a rounded cell morphology known as SM with well-differentiated phenotype (SMWD).
This morphology is associated with a less aggressive disease course and a mast cell function more similar to normal. Patients with the other mutations had a cell marker called CD25 present.
“Our findings provide new molecular insights into SMWD pathogenesis that should improve diagnostic accuracy and inform the therapeutic application of, and response to, tyrosine kinase inhibitors targeting KIT,” the authors wrote.
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