Identification of exosomes in non-Hodgkin B-cell lymphomas. Prognostic usefulness in patients treated with rituximab-chemotherapy: a prospective, multicenter correlation study by the Spanish Lymphoma Oncology Group (GOTEL)

To determine the presence of mRNAs (C-MYC, BCL-XL, BCL-6, NF-&kgr;&bgr;, PTEN and AKT) in exosomes of plasma from patients with B-Cell Lymphoma, and its relationship with their response to rituximab-based chemotherapy and survival. Exosomes were isolated of 98 patients with B-cell Lymphoma and 68 healthy controls. mRNAs were analyzed by quantitative PCR. 31 post-treatment samples were also studied. Exosome levels were not associated with response to treatment and outcome of patients. In general series and follicular lymphomas (FL), presence of AKT mRNA was associated with non-response to rituximab-based treatment. Patients with first relapse or disease progression showed a lower percentage of presence of PTEN and BCL-XL mRNA. Presence of BCL-6 mRNA was associated with high rate of death of patients. Absence of PTEN mRNA, in general series, and presence of C-MYC mRNA, in FL, was associated with short Progression-Free Survival. BCL-6 and C-MYC mRNA were independent prognostic variables for OS. C-MYCmRNA interacted with response to treatment, giving prognostic value for OS in non responsive patients. In post-treatment samples, presence of BCL-XL mRNA was associated with high rate of death; and appearance of BCL-6 mRNA and loss of PTENmRNA were associated with non-response to treatment. It is possible to identify exosomes in plasma of lymphoma patients. This may assist in prognosis, both at the start of treatment and during follow-up, and in identification of those patients at greater risk of progression. In both situations, the presence of BCL-6 identifies the patients with worse prognosis.