LNA Anti-Microrna-155: a Novel Therapeutic Strategy In Waldenstrom Macroglobulinemia and Chronic Lymphocytic Leukemia

We and others have previously demonstrated that microRNA-155 (miR-155) is overexpressed in patients with Waldenstrom's Macroglobulinemia (WM) and Chronic lymphocytic leukemia (CLL) compared to healthy subjects; indicating that miR-155 may play a crucial role in regulating the pathogenesis of these diseases. We therefore evaluated the role of the novel locked nucleic acid (LNA) antimiR against miR-155 in WM and CLL-derived cell lines.

WM and CLL-derived cell lines (BCWM.1, MEC1) have been treated with 20μM antisense LNA antimiR-155 or scramble probe (Santaris Pharma, Hørsholm, Denmark). Efficiency of delivered LNA oligos into cells was determined by using FAM-labeled LNA, followed by Flow cytometry (FACS). Survival and cell proliferation were assessed by MTT assay and thymidine uptake, respectively. Serum levels of miR-155 from peripheral blood of WM patients or healthy subjects and the level of miR-155-targeted genes were detected by quantitative RT-PCR (qPCR).

Efficiency of delivered LNA oligos into both WM and CLL-derived cell lines was higher than 90%. LNA antimiR-155 reduced proliferation of WM and CLL-derived cell lines, as compared to LNA scramble probe used as a control. In contrast, LNA antimiR-155 did not exert any effect on survival of them. We demonstrated increased expression of miR-155-targeted genes, such as CEBPβ, SOCS1, and TP53DINP1 in WM cells upon LNA antimiR-155 treatment. Moreover, we found miR-155 could be detected in peripheral blood serum of WM patients, but not the serum of healthy subjects.

These data provide preclinical evidence for using the novel antisense LNA antimiR-155 in WM and CLL. Moreover, serum levels of miR-155 could potentially be used as a biomarker in patients with WM.

No relevant conflicts of interest to declare.