Please cite this article in press as: Bataille R, et al., CD117 (c-kit) is aberrantly expressed in a subset of MGUS and multiple myeloma with unexpectedly good prognosis, Leuk Res (2007), doi:10.1016/j.leukres.2007.07.016 ARTICLE IN PRESS LR-2840; No. of Pages 4 Leukemia Research xxx (2007) xxx–xxx CD117 (c-kit) is aberrantly expressed in a subset of MGUS and multiple myeloma with unexpectedly good prognosis R´ egis Bataille a,∗ , Catherine Pellat-Deceunynck a , Nelly Robillard b , Herv´ e Avet-Loiseau a,b , Jean-Luc Harousseau c , Philippe Moreau c,∗ a INSERM UMR 601, Institute of Biology, Nantes, France b Central Laboratory of Haematology, Institute of Biology, Nantes, France c Department of Clinical Haematology, CHU Hˆ otel-Dieu, Nantes, France Received 21 February 2007; received in revised form 17 July 2007; accepted 23 July 2007 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. © 2007 Elsevier Ltd. All rights reserved. Keywords: CD117; Myeloma 1. Introduction CD117 (kit) is an essential haematopoietic growth factor receptor with tyrosine-kinase activity. Kit-mediated signal transduction is critical for the normal development and sur- vival mainly of haematopoietic progenitor cells (reviewed in [1]). Note that within malignant cells, the detection of CD117 is of paramount relevance for the diagnosis of gas- trointestinal stromal tumours (GIST). Indeed, 95% of GIST are CD117 positive. The vast majority of all other sarcomas, carcinomas and even lymphomas are CD117-, whereas nor- mal epithelial tissues like breast tissues stain positively [1]. Preliminary studies have shown that some MM aberrantly ∗ Corresponding authors. Tel.: +33 2 40 08 47 68; fax: +33 2 40 08 47 78. E-mail addresses: r-bataille@nantes.fnclcc.fr (R. Bataille), philippe.moreau@chu-nantes.fr (P. Moreau). do express CD117, since normal PC do not express CD117 [2]. However, no study evaluating the prognostic impact of the aberrant expression of CD117 in patients with MM was available yet. We here confirm this aberrant expression of CD117 in MM at diagnosis. Furthermore, we show that it is unexpectedly associated with a more indolent disease. This is in agreement with the fact that, surprisingly enough, MGUS also frequently express CD117. 2. Patients and methods 2.1. Patients One hundred and twenty-one consecutive patients with either newly diagnosed MM (n = 83) or MM in relapse (n = 38), as well as 12 individuals with MGUS and 23 human 0145-2126/$ – see front matter © 2007 Elsevier Ltd. All rights reserved. doi:10.1016/j.leukres.2007.07.016