PCR helps to create potential myeloma blood test

Researchers from the NIH, the National Cancer Institute (NCI), and the Dana-Farber Cancer Institute of Harvard Medical School have used the polymerase chain reaction (PCR) to help to create a potential multiple myeloma diagnostic. The results were published in the Journal of Molecular Diagnostics.

DNA double helix

Multiple myeloma is a cancer of the bone marrow with a five-year relative survival rate of 69% at stage 1, falling to 45% in advanced cases. However, only 5% of cases are diagnosed in the earliest stages. Some people with monoclonal gammopathy of undetermined significance (MGUS), an asymptomatic condition where the body produces high levels of antibodies, and smouldering myeloma (SMM), a slow-growing form of myeloma, will go on to develop multiple myeloma. Being able to identify these individuals could improve outcomes and cut long-term healthcare costs.

“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,” says Katherine R Calvo, MD, PhD, of the National Institutes of Health.

In multiple myeloma, the microenvironment of the bone marrow has been thought to play a role on the biology of the disease. Using microarrays and quantitative real-time PCR (qPCR), the researchers analysed blood and bone marrow from controls and people with multiple myeloma. They found 11 miRNAs (non-coding RNA fragments that regulate gene expression and modulate the production of specific proteins) in the bone marrow that could indicate multiple myeloma. Of these, six were decreased in both bone marrow, serum and plasma samples – let-7a, let-7b, let-7i, miR-15b, miR-16 and miR-20a.

Looking at serum samples from patients with MGUS and smouldering myeloma, only four of the 11 miRNAs 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,” says Calvo.

Eight of the 11 miRNAs were decreased in smouldering plasma samples. However, three were significantly reduced only in the myeloma samples, suggesting that down-regulation 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 down-regulated 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,” says Calvo.

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