|
|||||
|
|
MET dysregulation is a hallmark of aggressive disease in multiple myeloma patients |
|
| Authors: | Alberto Rocci Manuela Gambella Simona Aschero Ileana Baldi Livio Trusolino Federica Cavallo Francesca Gay Alessandra Larocca Valeria Magarotto Paola Omedè Gianluca Isaia Andrea Bertotti Anna M. Liberati Lucio Catalano Luca De Rosa Pellegrino Musto Roberto Vallone Antonietta Falcone Daniela Drandi Marco Ladetto Paolo M. Comoglio Mario Boccadoro Antonio Palumbo |
| Affiliation: | 1. Myeloma Unit, Division of Haematology, University of Torino, Azienda Ospedaliera Città della Salute e della Scienza di Torino, , Torino, Italy;2. Unit of Biostatistics, Public Health and Epidemiology, Department of Cardiac, Thoracic and Vascular Sciences, University of Padova, , Padova, Italy;3. Laboratory of Molecular Pharmacology, Institute for Cancer Research and Treatment (IRCC), , Candiolo (Torino), Italy;4. Department of Oncological Sciences, University of Torino School of Medicine, , Candiolo (Torino), Italy;5. Division of Geriatric, Department of Clinical and Biological Sciences, S. Luigi Gonzaga Hospital, University of Torino, , Torino, Italy;6. Department of Oncohaematology, University of Perugia, Santa Maria Hospital, , Terni, Italy;7. Divisione di Ematologia, Università Federico II, , Napoli, Italy;8. Haematology and Bone Marrow Transplantation Unit, Azienda Ospedaliera San Camillo‐Forlanini, , Rome, Italy;9. Department of Onco‐Haematology, IRCCS, Referral Cancer Center of Basilicata, , Rionero in Vulture (Pz), Italy;10. Servizio di Immunoematologia e Trasfusione, DH Ematologia Azienda Ospedaliera G. Rummo, , Benevento, Italy;11. Divisione di Ematologia, Casa Sollievo della Sofferenza, , San Giovanni Rotondo, Italy;12. Division of Haematology, University of Torino, Azienda Ospedaliera Città della Salute e della Scienza di Torino, , Torino, Italy |
| Abstract: | Abnormal activation of MET/HGF (Hepatocyte Growth Factor) pathway has been described in several tumours and increased HGF plasmatic levels have been detected in patients with aggressive multiple myeloma (MM). MET and HGF mRNA expression was investigated in 105 samples of purified plasma cells derived from newly diagnosed MM patients treated with bortezomib‐based induction therapy. Gene expression was compared with response to therapy and clinical outcome. MET gene copy number was also evaluated. MET mRNA expression was higher in CD138+ than in CD138? cells (median 76·90 vs. 11·24; P = 0·0009). Low MET mRNA expression characterized patients with better response (complete response or very good partial response) compared to other patients (median 56·10 vs. 134·83; P = 0·0006). After a median follow‐up of 50 months, patients with high MET mRNA expression displayed a worse progression‐free survival (PFS; P = 0·0029) and overall survival (OS; P = 0·0023) compared to those with low MET mRNA levels. Patients with both high MET mRNA expression and high β2‐microglobulin level (>5·5 mg/l) had further worse median PFS (P < 0·0001) and OS (P < 0·0001). Patients carrying 4 MET gene copies (8 out of 82, 9·8%) also had a short PFS. High MET mRNA expression identifies patients with dismal PFS and OS and the combination with high β2‐microglobulin further characterizes patients with worse outcome. |
| Keywords: | multiple myeloma MET hepatocyte growth factor biomarker prognostic factor |