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 center dot 90 vs. 11 center dot 24; P=0 center dot 0009). Low MET mRNA expression characterized patients with better response (complete response or very good partial response) compared to other patients (median 56 center dot 10 vs. 134 center dot 83; P=0 center dot 0006). After a median follow-up of 50months, patients with high MET mRNA expression displayed a worse progression-free survival (PFS; P=0 center dot 0029) and overall survival (OS; P=0 center dot 0023) compared to those with low MET mRNA levels. Patients with both high MET mRNA expression and high beta 2-microglobulin level (>5 center dot 5mg/l) had further worse median PFS (P<0 center dot 0001) and OS (P<0 center dot 0001). Patients carrying 4 MET gene copies (8 out of 82, 9 center dot 8%) also had a short PFS. High MET mRNA expression identifies patients with dismal PFS and OS and the combination with high beta 2-microglobulin further characterizes patients with worse outcome.