Serum MicroRNA Profiles May Help Detect and Monitor Multiple Myeloma Progress

A simple blood test may be able to detect and monitor patients at high risk for multiple myeloma (MM).

A simple blood test may be able to detect and monitor patients at high risk for multiple myeloma (MM).

Researchers at the NIH have found that the bone marrow (BM) microenvironment of MM appears to play a role in the biology of disease. Through careful investigation, they uncovered that the extracellular BM microenvironment in MM contains a unique microRNA (miRNA) signature detectable by miRNA microarray and quantitative real-time PCR.

The study published in The Journal of Molecular Diagnostics, report that abnormal levels of miRNAs detected in the BM of MM patients may be detectable in peripheral blood and used to help predict myeloma onset and track its progression from earlier asymptomatic stages.1  Several precursor conditions of myeloma have been recognized, including monoclonal gammopathy of undetermined significance (MGUS) and smoldering myeloma (SMM). Although 1% of individuals with MGUS advance to myeloma each year, the rate is 10% for those with SMM.

“Currently there is no single factor that can predict patients with MGUS or SMM who are likely to progress to myeloma. A biomarker of disease progression in the peripheral blood could assist in the early identification of patients evolving to multiple myeloma,” said lead investigator Katherine Calvo, MD, PhD, who is of the Hematology Section of the Department of Laboratory Medicine of the National Institutes of Health (NIH) Clinical Center, Bethesda, Md.

Dr. Calvo and her colleagues at the Dana-Farber Cancer Institute of Harvard Medical School analyzed BM, plasma, and serum samples from healthy controls and patients with myeloma, as well as from patients with MGUS and SMM.

An analysis of fluid from the bone marrow of 20 patients with myeloma resulted in the identification of 111 miRNAs that showed a two-fold or greater difference from levels observed in eight control samples. The researchers found that approximately 60% of the miRNAs were downregulated and 38% were upregulated. Further analysis revealed a unique miRNA signature indicative of myeloma. The bone-marrow signature included eight members of the let-7 family of miRNAs, each of which showed significant decreases ranging from six-to 17-fold in patients with myeloma.

In an analysis of serum samples in 17 patients with MGUS, 17 with SMM, 13 with myeloma, and 12 healthy controls, the researchers made an interesting discovery. They found that only four of the 11 miRNAs (36%) that were reduced in the myeloma serum samples were lower in the MGUS samples. “This suggests that aberrant expression of these four miRNAs may be associated with early events in plasma cell neoplasia,” said Dr. Calvo.

Eight of the 11 (73%) miRNAs were decreased in SMM plasma samples. However, three (27%) were significantly reduced only in the myeloma samples, suggesting that downregulation of this group of miRNAs may be related to later events during evolution from precursor disease to myeloma.

“Our findings suggest that the antiproliferative and proapoptotic miRNAs, such as the let-7 family members, are downregulated in multiple myeloma’s microenvironment. These findings suggest that measuring expression of miRNAs associated with myeloma progression in the peripheral blood may hold promise for predicting disease progression in MGUS and SMM,” explained Dr. Calvo.