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MET dysregulation is a hallmark of aggressive disease in multiple myeloma patients
Author(s) -
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
Publication year - 2014
Publication title -
british journal of haematology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.907
H-Index - 186
eISSN - 1365-2141
pISSN - 0007-1048
DOI - 10.1111/bjh.12719
Subject(s) - hepatocyte growth factor , medicine , multiple myeloma , bortezomib , beta 2 microglobulin , progression free survival , gene expression , progressive disease , messenger rna , gastroenterology , oncology , overall survival , chemotherapy , biology , gene , receptor , biochemistry
Summary Abnormal activation of MET / HGF ( H epatocyte G rowth F actor) 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 m RNA 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 m RNA expression was higher in CD 138 + than in CD 138 − cells (median 76·90 vs. 11·24; P = 0·0009). Low MET m RNA 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 m RNA expression displayed a worse progression‐free survival ( PFS ; P = 0·0029) and overall survival ( OS ; P = 0·0023) compared to those with low MET m RNA levels. Patients with both high MET m RNA 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 m RNA expression identifies patients with dismal PFS and OS and the combination with high β2‐microglobulin further characterizes patients with worse outcome.