CD117 (c-kit) is aberrantly expressed in a subset of MGUS and multiple myeloma with unexpectedly good prognosis

Abstract

CD117 (c-kit) was evaluated on normal plasma cells (PC) ( n = 10), PC of individuals with monoclonal gammopathy of undetermined significance (MGUS, n = 12), malignant PC from patients with multiple myeloma (MM) either at diagnosis ( n = 83) or relapse ( n = 38) and on 23 human myeloma cell lines (HMCL). Whereas CD117 is never expressed in normal PC, it is expressed in 50% of MGUS ( p = 0.015). Furthermore, 33% of MM at diagnosis do express CD117, as opposed to 8% of those in relapse ( p = 0.003). Finally, CD117 was never found in HMCL. CD117 expression was associated with a better prognosis: overall survival was 93% at 4 years in CD117+ MM versus 64% in CD117− MM ( p = 0.05). Conversely, lack of CD117, but also high beta-2 microglobulin, t(4;14) and CD221 (IGF-1R) expression were associated with a poorer prognosis. Multivariate analysis revealed that CD117− patients were those with CD221 and t(4;14) and had the poorest prognosis. In conclusion, CD117 (c-kit) is aberrantly expressed on a subset of MGUS and MM with a more indolent presentation and is functionally antinomic to CD221 (IGF-1R). CD117 expression could be related to a specific oncogenic pathway in MM.