MET dysregulation is a hallmark of aggressive disease in multiple myeloma patients. (23rd January 2014)

• Record Type: Journal Article
• Authors: Rocci, Alberto; Gambella, Manuela; Aschero, Simona; Baldi, Ileana; Trusolino, Livio; Cavallo, Federica; Gay, Francesca; Larocca, Alessandra; Magarotto, Valeria; Omedè, Paola; Isaia, Gianluca; Bertotti, Andrea; Liberati, Anna M.; Catalano, Lucio; De Rosa, Luca; Musto, Pellegrino; Vallone, Roberto; Falcone, Antonietta; Drandi, Daniela; Ladetto, Marco; Comoglio, Paolo M.; Boccadoro, Mario; Palumbo, Antonio
• Is Part Of: British journal of haematology. Volume 164:Number 6(2014:Mar.)
• Page Start: 841
• Page End: 850
• Publication Date: 2014-01-23
• Subjects: Hematology -- Periodicals; Blood -- Diseases -- Periodicals; 616.15
• DOI: 10.1111/bjh.12719
• Languages: English
• ISSNs: 0007-1048

Abstract

<abstract abstract-type="main" id="bjh12719-abs-0001"> <title>Summary</title> <p>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). <italic>MET</italic> and <italic>HGF</italic> 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. <italic>MET</italic> gene copy number was also evaluated. <italic>MET</italic> mRNA expression was higher in CD138<sup>+</sup> than in CD138<sup>−</sup> cells (median 76·90 vs. 11·24; <italic>P</italic> = 0·0009). Low <italic>MET</italic> mRNA expression characterized patients with better response (complete response or very good partial response) compared to other patients (median 56·10 vs. 134·83; <italic>P</italic> = 0·0006). After a median follow‐up of 50 months, patients with high <italic>MET</italic> mRNA expression displayed a worse progression‐free survival (PFS;<italic> P</italic> = 0·0029) and overall survival (OS;<italic> P</italic> = 0·0023) compared to those with low <italic>MET</italic> mRNA levels. Patients with both high <italic>MET</italic> mRNA expression and high β2‐microglobulin level (>5·5 mg/l) had further worse median PFS (<italic>P</italic> < 0·0001) and OS (<italic>P</italic> < 0·0001). Patients carrying 4 <italic>MET</italic> gene copies (8 out of 82, 9·8%) also had a short PFS. High <italic>MET</italic> mRNA expression identifies patients with dismal PFS and OS and the combination with high β2‐microglobulin further characterizes patients with worse outcome.</p> </abstract>