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)

Abstract

Background: To determine the presence of mRNAs (C-MYC, BCL-XL, BCL-6, NF-kappabeta, 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. Methods: 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. Results: 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. Conclusions: 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.