Dysregulation of miRNAs in AL amyloidosis

Abstract

Bone marrow plasma cells (BMPCs) were purified using anti-CD138 immunomagnetic beads, from aspirates obtained with permission of the Boston University Medical Campus Institutional Review Board, from patients with immunoglobulin light chain (AL) amyloidosis and from controls. Expression levels of MicroRNAs (miRNAs) were compared by microarray; 10 were found to be increased more than 1.5-fold. These results were confirmed using stem-loop RT-qPCR for the most highly upregulated miRNAs, miR-148a, miR-26a, and miR-16. miR-16, a micro-RNA linked to other hematopoietic diseases, was significantly increased in the AL group at diagnosis, and also in treated patients with persistent monoclonal plasma cells in the bone marrow, but not in patients who achieved a hematologic remission after therapy. miR-16 can be derived from the miR-16-1/mirR-15, a cluster on chromosome 13 or the miR-16-2/miR-15b cluster on chromosome 3. The expression of miR-15b was much higher than miR-15a in both AL and control BMPC, suggesting that miR-16 in plasma cells is mainly derived from miR-16-2/miR-15b. The anti-apoptosis gene BCL-2, a putative target mRNA that can be downregulated by miR-16, was expressed in BMPCs from AL patients, despite elevated levels of miR-16. Our data suggests that miRNAs are dysregulated in clonal plasma cells in AL amyloidosis and may be potentially useful as biomarkers of disease.

Keywords::

• Amyloidosis
• plasma cell
• micro-RNA
• BCL-2
• biomarker

Acknowledgements

The authors thank Drs. Samir Amin, YuXia Cao, Beth Hovey, Jining Lu, Nikhil Munshi, Martha Skinner, and Jennifer Ward for helpful discussions. They gratefully acknowledge the participation of amyloidosis patients in this study, and the assistance of the clinical, administrative, and laboratory staff of the Amyloid Treatment and Research Program and the Gerry Amyloid Research Laboratory.

Declaration of interest: The authors have no conflicts to disclose. The authors alone are responsible for the content and preparation of the manuscript. The authors are employees of Boston University and Boston Medical Center. The work was funded by a P01 from NHLBI HL068705 (D. Seldin), by a T32 from NHLBI HL007501 (L. Weng), and by gifts from the Gruss and Wildflower Foundations.