Photo by Daniel Sone
Research published in Leukemia suggests bone marrow mesenchymal stem cells (BMMSCs) are altered in monoclonal gammopathy of undetermined significance (MGUS) as well as in multiple myeloma (MM).
This discovery indicates that changes in the bone marrow needed for MM to grow have already taken hold in patients with MGUS, raising the possibility that early medical intervention could prevent the development of MM.
“It is now clear that the bone marrow of patients with MGUS, traditionally thought of as a benign condition, is significantly different to that of healthy individuals,” said study author Daniel Tennant, PhD, of the University of Birmingham in the UK.
“The bone marrow environment in these patients appears capable of supporting cancer growth, even though the majority of patients will not progress to myeloma. While this research is in the early stages, it offers the exciting possibility that early intervention could potentially delay or even prevent cancer development.”
With this study, Dr Tennant and his colleagues found that, early on in MGUS development, BMMSCs change their behavior and become more supportive of cancer growth.
The team found that a key gene, PADI2, becomes particularly overactive in BMMSCs, which leads to overproduction of the signaling molecule interleukin-6 (IL-6).
BMMSCs release IL-6 into the bone marrow, where it binds with receptors on the surface of cancerous plasma cells, instructing them to multiply rapidly and resist cell death signals.
It is already known that high levels of IL-6 in a patient’s bone marrow significantly reduces the effectiveness of the drug bortezomib.
The researchers believe that drugs designed to target the PADI2 gene in MGUS and MM patients could significantly reduce the supportive signaling that MM cells depend on, and such drugs may increase the effectiveness of current treatments.
The team also noted that the PADI2 gene has been linked to other types of cancer, rheumatoid arthritis, Alzheimer’s disease, and autoimmune disease. So any drug developed could have wider applications beyond MM treatment.
“There is an urgent need for new treatments for myeloma, which, as well as being largely incurable, can have a devastating impact on quality of life,” said Alasdair Rankin, director of research at the blood cancer charity Bloodwise, which helped to fund this study.
“With an increasing elderly population, MGUS and myeloma are only going to become more common. Drugs designed to remove the support system myeloma uses to grow could be an effective way of treating the disease, or even preventing it altogether.”
