Cancer researchers find underlying cause of certain myelomas

Researchers have identified the cause of myeloma related to Gaucher disease, according to a study published online February 12, 2016 in The New England Journal of Medicine. This finding could change the way this myeloma and other cancers are treated, researchers predicted.

The risk of myeloma is markedly higher among patients with Gaucher disease, a rare lysosomal storage disorder, than in the general population. Indeed, myeloma is emerging as a leading cause of cancer-related death in patients with Gaucher disease, researchers noted.

Previous studies have provided evidence that antigens might drive the increase in plasma cells in the etiology of multiple myeloma, but researchers haven’t been able to identify which antigens these are. Because lipid disorders such as Gaucher disease and obesity are associated with an increased risk of myeloma, researchers suspected that lipids were involved in the pathogenesis.

In this investigation, the researchers used tissue and blood samples from humans and mice to show that specific lipids—lyso-glucosylceramide (LGL1) and lysophosphatidylcholine (LPC)—trigger gammopathies in both mice and patients with Gaucher disease, and that the antibodies made by tumor cells in nearly a third of these patients are directed against such lipids.

“Understanding the origin of any cancer has several implications for how to best prevent it,” said senior author Madhav Dhodapkar, MD, the Arthur H. and Isabel Bunker Professor of Medicine and Immunobiology, and chief of Hematology at Yale University School of Medicine, in New Haven, CT.

“These studies set the stage for newer approaches to lower the levels of these lipids in patients with Gaucher disease and others with precursors for myeloma,” Dr. Dhodapkar said. “Potentially, this could be achieved with drugs or lifestyle changes to reduce the levels of lipids to lower the risk of cancer.”

Further studies in larger cohorts are needed to confirm these findings and to better define the genetics of lipid-reactive myeloma, the researchers noted. That research could lead to clinical trials to find out whether lowering levels of bioactive lipids will reduce the risk of this myeloma and other cancers, they added.