CD117 (c-kit) is aberrantly expressed in a subset of MGUS and multiple myeloma with unexpectedly good prognosis.
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.
Bataille
Régis
R
INSERM UMR 601, Institute of Biology, Nantes, France. r-bataille@nantes.fnclcc.fr
Pellat-Deceunynck
Catherine
C
Robillard
Nelly
N
Avet-Loiseau
Hervé
H
Harousseau
Jean-Luc
JL
Moreau
Philippe
P
D000368:Aged; D045744:Cell Line, Tumor; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D009101:Multiple Myeloma / Q000276:immunology*; D010265:Paraproteinemias / Q000276:immunology*; D011379:Prognosis; D019009:Proto-Oncogene Proteins c-kit / Q000378:metabolism*; D016019:Survival Analysis
D019009:Proto-Oncogene Proteins c-kit