MET dysregulation is a hallmark of aggressive disease in multiple myeloma patients.
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.
Myeloma Unit, Division of Haematology, University of Torino, Azienda Ospedaliera Città della Salute e della Scienza di Torino, Torino, Italy.
Alberto
A
Rocci
Manuela
M
Gambella
Simona
S
Aschero
Ileana
I
Baldi
Livio
L
Trusolino
Federica
F
Cavallo
Francesca
F
Gay
Alessandra
A
Larocca
Valeria
V
Magarotto
Paola
P
Omedè
Gianluca
G
Isaia
Andrea
A
Bertotti
Anna M
AM
Liberati
Lucio
L
Catalano
Luca
L
De Rosa
Pellegrino
P
Musto
Roberto
R
Vallone
Antonietta
A
Falcone
Daniela
D
Drandi
Marco
M
Ladetto
Paolo M
PM
Comoglio
Mario
M
Boccadoro
Antonio
A
Palumbo
D000368:Aged; D000369:Aged, 80 and over; D014408:Biomarkers, Tumor / Q000378:metabolism; D005260:Female; D017228:Hepatocyte Growth Factor / Q000096:biosynthesis / Q000097:blood / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D008297:Male; D008875:Middle Aged; D009101:Multiple Myeloma / Q000235:genetics / Q000378:metabolism* / Q000473:pathology* / Q000628:therapy; D011379:Prognosis; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism
D014408:Biomarkers, Tumor; D012333:RNA, Messenger; D017228:Hepatocyte Growth Factor
MET; biomarker; hepatocyte growth factor; multiple myeloma; prognostic factor