ELEVATED EXPRESSION OF THE PROTOONCOGENE C-KIT IN PATIENTS WITH MASTOCYTOSIS

The stem cell factor (SCF)c-kit receptor interaction plays a critical role in the development and survival of mast cells, Several studies ha ve also associated c-kit receptor mutations with the human diseases, m astocytosis and piebaldism. Overexpression of c-kit has been reported to be associated with myeloproliferative disorders and myelodysplastic syndromes. Using peripheral blood mononuclear cells (PBMCs) from II p atients with indolent mastocytosis (category I), mastocytosis with an associated hematologic disorder (category II), or aggressive mastocyto sis (category III); a patient with CMML unassociated with mastocytosis , and PBMCs from 13 normal subjects, we examined the level of expressi on of c-kit mRNA along with other c-kit isoforms to determine if overe xpression of the c-kit receptor was associated with mastocytosis. Usin g quantitative competitive PCR, c-kif mRNA levels on average were foun d to be statistically elevated in the five patients with mastocytosis with an associated hematologic disorder and in the patient with aggres sive mastocytosis as compared with controls, but not elevated in patie nts with indolent mastocytosis, The relative mRNA expression for the t wo c-kit isoforms was not significantly different in the mastocytosis patients compared with controls. This demonstration of the overexpress ion of c-kit mRNA in mastocytosis, and particularly those patients wit h clinical evidence of myelodysplastic syndrome, adds evidence to supp ort the conclusion that mastocytosis, at least in some patients, is a feature of myelodysplasia; and suggests that determination of c-kit mR NA expression in PBMCs may provide an additional approach to assessing prognosis.