PURPOSE: Plasma cell leukemia (PCL) is a rare form of plasma cells dyscrasia that presents either as a progression of previously diagnosed multiple myeloma (MM), namely secondary PCL, or as initial manifestation of disease, namely primary PCL (pPCL). Although presenting signs and symptoms include those seen in MM, pPCL is characterized by several aspects that define more aggressive course. Herein, we have investigated the transcriptome of pPCLs and correlated differential expression profiles with outcome, to provide insights into the biology of the disease. Experimental design: The expression profiles of 21 newly-diagnosed pPCLs included in a multicenter prospective clinical trial were generated using high-density microarray, then evaluated in comparison with a representative series of multiple myeloma (MM) patients and in association with clinical outcome. RESULTS: All but one of the pPCLs had one of the main IGH translocations, whose associated transcriptional signatures resembled those observed in MM. A 503-gene signature distinguished pPCL from MM, from which emerged 26 genes whose expression trend was associated with progressive stages of plasma cells dyscrasia in a large dataset from multiple institutions, including samples from normal donors throughout PCL. Finally, three genes were identified having expression levels correlated with response to the first-line treatment with lenalidomide/dexamethasone, whereas a 27-gene signature was associated with overall survival independently of molecular alterations, hematological parameters and renal function. CONCLUSIONS: Overall, our data contribute to a fine dissection of pPCL and may provide novel insights into the molecular definition of patients with poorer prognosis.
Transcriptional characterization of a prospective series of primary plasma cell leukemia revealed signatures associated with tumor progression and poorer outcome / K. Todoerti, L. Agnelli, S. Fabris, M. Lionetti, G. Tuana, L. Mosca, L. Lombardi, V. Grieco, G. Bianchino, F. D'Auria, T. Statuto, C. Mazzoccoli, L. De Luca, M.T. Petrucci, F. Morabito, M. Offidani, F. Di Raimondo, A. Falcone, P. Omedè, P. Tassone, M. Boccadoro, A. Palumbo, A. Neri, P. Musto. - In: CLINICAL CANCER RESEARCH. - ISSN 1078-0432. - 19:12(2013 Apr 18), pp. 3247-3258.
|Titolo:||Transcriptional characterization of a prospective series of primary plasma cell leukemia revealed signatures associated with tumor progression and poorer outcome|
TODOERTI, KATIA (Primo)
AGNELLI, LUCA (Secondo)
NERI, ANTONINO (Penultimo)
|Settore Scientifico Disciplinare:||Settore MED/15 - Malattie del Sangue|
|Data di pubblicazione:||18-apr-2013|
|Digital Object Identifier (DOI):||http://dx.doi.org/10.1158/1078-0432.CCR-12-3461|
|Appare nelle tipologie:||01 - Articolo su periodico|