Inhibition of pathologic immunoglobulin-free light chain production by small interfering RNA molecules.

Experimental Hematology
Jonathan E PhippsJonathan S Wall

Abstract

Morbidity and mortality occurring in patients with multiple myeloma, AL amyloidosis, and light chain deposition disease can result from the pathologic deposition of monoclonal immunoglobulin light chains (LCs) in kidneys and other organs. To reduce synthesis of such components, therapy for these disorders typically has involved antiplasma cell agents; however, this approach is not always effective and can have adverse consequences. We have investigated another means to achieve this objective; namely, RNA interference. SP2/O mouse myeloma cells were stably transfected with a construct encoding a λ6 LC (Wil) under control of the cytomegalovirus promoter, while λ2-producing myeloma cell line RPMI 8226 was purchased from the American Type Culture Collection (Manassas, VA, USA). Both were treated with small interfering RNA directed specifically to the V, J, or C portions of the molecules and then analyzed by enzyme-linked immunosorbent assay, flow cytometry, and real-time polymerase chain reaction. Transfected cells were found to constitutively express detectable quantities of messenger RNA and protein Wil and, after exposure to small interfering RNAs, an ∼ 40% reduction in messenger RNA and LC production was evidenced at 48 hours. ...Continue Reading

Citations

May 13, 2011·Gene Therapy·B M HoveyD C Seldin
Aug 28, 2013·Nature Reviews. Nephrology·Julian D Gillmore, Philip N Hawkins
Nov 8, 2011·American Journal of Physiology. Heart and Circulatory Physiology·Jian GuanRonglih Liao
Apr 28, 2012·Blood Reviews·Angela DispenzieriFrancis Buadi
Jan 9, 2013·British Journal of Haematology·Moshe E Gatt, Giovanni Palladini
Jul 2, 2015·Current Allergy and Asthma Reports·Jonathan A Bernstein, Umesh Singh
Mar 4, 2017·Heart·Brett W Sperry, W H Wilson Tang
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Aug 20, 2016·Nephrology, Dialysis, Transplantation : Official Publication of the European Dialysis and Transplant Association - European Renal Association·Mario Nuvolone, Giampaolo Merlini

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