MicroRNA Analysis in the Cerebrospinal Fluid and Blood Serum of Lymphoma Patients At Diagnosis and in Response to Therapy,

Abstract 3663

MicroRNAs are non-coding RNAs (19–23nt) that negatively regulate expression by interference with the translation or RNA stability of up to hundreds of targets. Tumors including leukemias and lymphomas are associated with deregulated expression of microRNAs (Volinia et al. 2010). Several microRNAs including miR-17-92 cluster members and miR-155 are overexpressed in lymphomas and showed promise in predicting relapse (Fabbri M et al. 2011). Unlike longer species of RNA, microRNAs are preserved and detectable in human fluids including serum, plasma and cerebrospinal fluid (CSF) (Baraniskin A. et al. 2011). We investigated abundance of microRNAs in the CSF and sera and tested whether their levels are associated with diagnosis or treatment of lymphomas. We studied patients with primary central nervous system lymphomas (PCNSL) (N=3) and systemic lymphomas either with CNS dissemination (N=3) or without (N=11). Histological type was predominantly diffuse large B cell lymphoma - DLBCL (N=13). Sera of a control group were also used. 200 uL of CSF and sera (both cell free) were used for total RNA isolation followed by PCR and the data were adjusted to levels of control microRNAs (miR-let-7a or miR-24). Our data demonstrate that the microRNAs of the miR-17-92 cluster (miR-19a, miR-20a, miR-92a) and miR-106b-25 cluster (miR-106b, miR-25) and miR-155 are detectable (unlike miR-106a, miR-18a) in both the CSF and sera. Particularly, miR-17-92 and miR-106b-25 are increased in CSF of the PCNSL and the systemic lymphomas with CNS involvement compared with systemic lymphomas without CNS involvement. Conversely, in the sera, expression of miR-17-92 is increased in systemic lymphomas compared to PCNSL and the control group. Next, we investigated the levels of these microRNAs in a patient with systemic DLBCL with CNS dissemination during the treatment (R-CHOP alternating with RMPV) resulting in complete remission. Analysis of the CSF and also of the sera (at 9 different time points within three months) revealed a gradual decrease (∼6 fold) of the levels of miR-19a, miR-20a, miR-92a, miR-106b, and miR-25. However, the levels of these microRNAs in the sera at the stage of complete remission were still 2 fold higher compared to controls. We conclude that measurement of microRNAs in both CSF and sera represents novel sensitive tool, additional to other approaches, for tumor detection and/or for estimation of the therapy efficacy. (Grants: NT10310-3/2009, MPO FR-TI2/509, NPVII 2B06077, MSM 0021620806, LC 06044, SVV-2011-262507)