Myeloma Development Might Be Stalled by Blocking Pathway from a Benign Condition, Study Says

Researchers at the University of Birmingham have found that blocking a specific mechanism in the benign condition monoclonal gammophaty of undetermined significance (MGUS) may prevent the development of multiple myeloma. The findings were published in the journal Leukemia in the study “Citrullination of histone H3 drives IL-6 production by bone marrow mesenchymal stem cells in MGUS and multiple myeloma.”

MGUS is an age-dependent condition that affects approximately 7 percent of people over the age of 85. Although it is generally seen as a benign condition, about 1 percent of patients with MGUS evolve into myeloma per year. But unfortunately there are currently no tests that help doctors predict which of these patients will actually develop myeloma, or when.

Myeloma cells are always confined to the bone marrow, suggesting they need support from other cells in that environment, often called bone marrow stromal cells. Now, investigators have found that in the early stages of MGUS development, these bone marrow stromal cells acquire characteristics that support cancer growth. In particular, they revealed that a gene called PADI2 is highly upregulated.

These findings are important because PADI2 activity can directly induce the expression of interleukin-6 (IL-6), a signaling molecule that has a major role in the establishment of the malignant cell phenotype through increasing resistance to cell death and promoting rapid cell growth. Also, IL-6 has been shown to promote resistance to the chemotherapeutic agent bortezomib.

“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,” Dr. Daniel Tennant, the study’s senior author, said in a press release.

“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,” he said.

Their results show that blocking PADI2 can decrease the expression of IL-6 and other factors involved in the development of multiple myeloma, suggesting that this approach may be used to reduce the supporting cues from the bone marrow microenvironment.

Therefore, targeting PADI2 may enhance the effectiveness of currently used treatments and may possibly be used to prevent the development of myeloma from MGUS condition.

“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 Dr. Alasdair Rankin, director of research at the blood cancer charity Bloodwise, that funded the research. “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.”