Photo by Graham Colm
New research has revealed a microRNA (miRNA) signature in the bone marrow of patients with multiple myeloma (MM) that is also detectable in peripheral blood.
Investigators believe this signature may mark the onset of MM and predict progression to MM in patients with monoclonal gammopathy of undetermined significance (MGUS) or smoldering myeloma (SMM).
This research has been published in The Journal of Molecular Diagnostics.
“Currently, there is no single factor that can predict patients with MGUS or SMM who are likely to progress to myeloma,” said Katherine R. Calvo, MD, PhD, of the National Institutes of Health in Bethesda, Maryland.
“A biomarker of disease progression in the peripheral blood could assist in the early identification of patients evolving to multiple myeloma.”
With this in mind, Dr Calvo and her colleagues studied miRNAs as possible biomarkers of MM. Previous research has shown increased levels of specific miRNAs in the blood and plasma of MM patients.
In this study, the investigators analyzed bone marrow, plasma, and serum samples from healthy controls and patients with MM, MGUS, or SMM.
The team analyzed fluid from the bone marrow of 20 patients with MM and identified 111 miRNAs that showed a 2-fold or greater difference from levels observed in 8 control samples. Sixty-nine of the miRNAs were downregulated, and 42 were upregulated.
Further analysis revealed a unique miRNA signature indicative of MM. The bone marrow signature included 8 members of the let-7 family of miRNAs, each of which showed significant decreases ranging from 6-fold to 17-fold (P<0.03) in patients with MM.
Other experiments revealed the miRNA profiles characteristic of MM in peripheral blood, serum, and plasma samples.
Using quantitative real-time PCR, the investigators identified 18 miRNAs that were significantly decreased in bone marrow MM samples. Of these, 11 (60%) miRNAs were also significantly decreased in serum samples, and 6 of the 11 were also found to be lower in plasma samples (including 3 members of the let-7 miRNA family).
The investigators further explored whether the miRNA pattern of MM in precursor diseases changes as the disease progresses. They analyzed serum samples in 17 patients with MGUS, 17 with SMM, 13 with MM, and 12 healthy controls.
Only 4 of the 11 miRNAs (36%) that were reduced in the MM serum samples were lower in the MGUS samples.
“This suggests that aberrant expression of these [4] miRNAs may be associated with early events in plasma cell neoplasia,” Dr Calvo said.
Eight of the 11 (73%) miRNAs were decreased in SMM plasma samples. However, 3 (27%) were significantly reduced only in the MM samples, suggesting that downregulation of this group of miRNAs may be related to later events during evolution from precursor disease to MM.
“Our findings suggest that the antiproliferative and proapoptotic miRNAs, such as the let-7 family members, are downregulated in multiple myeloma’s microenvironment,” Dr Calvo said.
“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.”
