The genetic and genomic background of multiple myeloma patients achieving complete response after induction therapy with bortezomib, thalidomide and dexamethasone (VTD)
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Carolina Terragna1, Daniel Remondini2, Marina Martello1, Elena Zamagni1, Lucia Pantani1, Francesca Patriarca3, Annalisa Pezzi1, Giuseppe Levi2, Massimo Offidani4, Ilaria Proserpio5, Giovanni De Sabbata6, Paola Tacchetti1, Clotilde Cangialosi7, Fabrizio Ciambelli8, Clara Virginia Viganò9, Flores Angela Dico1, Barbara Santacroce1, Enrica Borsi1, Annamaria Brioli1, Giulia Marzocchi1, Gastone Castellani2, Giovanni Martinelli1, Antonio Palumbo10, Michele Cavo1
1”Seràgnoli” Institute of Hematology, Department of Experimental, Diagnostic and Specialty Medicine (DIMES), Bologna University School of Medicine, Bologna, Italy
2Department of Physics and Astronomy (DIFA), Bologna University, Bologna, Italy
3Clinica Ematologica, DISM, University of Udine, Udine, Italy
4Clinica di Ematologia, A.O.U. Ospedali Riuniti di Ancona, Ancona, Italy
5U.O Oncologia Medica, Ospedale di Circolo e Fondazione Macchi, Varese, Italy
6Ematologia Clinica, A.O.U. Ospedali Riuniti, Trieste, Italy
7Hematology Division UTMO, Azienda “Ospedali Riuniti Villa Sofia-Cervello” Presidio Ospedaliero V.Cervello, Palermo, Italy
8S.C.Oncologia Medica, A.O. Sant’Antonio Abate, Gallarate, Varese, Italy
9Unità Operativa di Ematologia, Istituti Ospitalieri di Cremona, Cremona, Italy
10Myeloma Unit, Division of Hematology, University of Torino, A.O.U. Città della Salute e della Scienza di Torino, Torino, Italy
Michele Cavo, e-mail: [email protected]
Keywords: multiple myeloma, gene expression profile, SNPs, VTD, complete response
Received: August 06, 2015 Accepted: September 16, 2015 Published: November 09, 2015
The prime focus of the current therapeutic strategy for Multiple Myeloma (MM) is to obtain an early and deep tumour burden reduction, up to the level of complete response (CR). To date, no description of the characteristics of the plasma cells (PC) prone to achieve CR has been reported. This study aimed at the molecular characterization of PC obtained at baseline from MM patients in CR after bortezomib-thalidomide-dexamethasone (VTD) first line therapy.
One hundred and eighteen MM primary tumours obtained from homogeneously treated patients were profiled both for gene expression and for single nucleotide polymorphism genotype. Genomic results were used to obtain a predictor of sensitivity to VTD induction therapy, as well as to describe both the transcription and the genomic profile of PC derived from MM with subsequent optimal response to primary induction therapy.
By analysing the gene profiles of CR patients, we identified a 5-gene signature predicting CR with an overall median accuracy of 75% (range: 72%–85%). In addition, we highlighted the differential expression of a series of genes, whose deregulation might explain patients’ sensitivity to VTD therapy. We also showed that a small copy number loss, covering 606Kb on chromosome 1p22.1 was the most significantly associated with CR patients.
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