MET dysregulation is a hallmark of aggressive disease in multiple myeloma patients

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 LadettoPaolo M. Comoglio, Mario Boccadoro, Antonio Palumbo

Research output: Contribution to journalArticle

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.

Original languageEnglish
Pages (from-to)841-850
Number of pages10
JournalBritish Journal of Haematology
Volume164
Issue number6
DOIs
Publication statusPublished - Mar 2014

Keywords

  • Biomarker
  • Hepatocyte growth factor
  • MET
  • Multiple myeloma
  • Prognostic factor

ASJC Scopus subject areas

  • Hematology

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  • Cite this

    Rocci, A., Gambella, M., Aschero, S., Baldi, I., Trusolino, L., Cavallo, F., Gay, F., Larocca, A., Magarotto, V., Omedè, P., Isaia, G., Bertotti, A., Liberati, A. M., Catalano, L., De Rosa, L., Musto, P., Vallone, R., Falcone, A., Drandi, D., ... Palumbo, A. (2014). MET dysregulation is a hallmark of aggressive disease in multiple myeloma patients. British Journal of Haematology, 164(6), 841-850. https://doi.org/10.1111/bjh.12719