Narrow subset of cells is responsible for metastasis in multiple myeloma, study finds

The study suggests that attacking those subsets with targeted drugs may degrade the disease's ability to spread throughout the bone marrow of affected patients, the authors say.

The discovery was made by developing a mouse model of the disease that enabled researchers to track which of 15 genetic groups – or subclones – of myeloma cells spread beyond their initial site in the animals' hind legs. By labeling the different subgroups with fluorescent dyes, researchers determined that just one of the subclones was responsible for the disease metastasis.

They then compared the pattern of gene abnormalities in the initial myeloma tissue and the metastatic tumors. They found that 238 genes were significantly less active in the latter group – comprising a gene “signature” of metastatic myeloma.

“Out of all the genes that were differently expressed in the two groups, we found 11 that played a functional role in metastasis and therefore may be drivers of the disease,” said Irene Ghobrial, MD, of Dana-Farber, the study's senior author. If future studies confirm that role, the genes may become targets for therapies that block myeloma metastasis, she added.

The lead author of the study is Yuji Mishima, PhD, of Dana-Farber. Co-authors are Michele Moschetta, MD, Salomon Manier, MD, Siobhan Glavey, MD, Michaela Reagan, PhD, Yawara Kawano, MD, PhD, Nikhil Munshi, MD, Kenneth Anderson, MD, and Aldo Roccaro, MD, PhD, of Dana-Farber; Jiantao Shi, PhD, and Winston Hide, PhD, of Harvard School of Public Health; Francois Mercier, MD, and David Scadden, MD, of Massachusetts General Hospital.

This study was supported by the Leukemia & Lymphoma Society (LLS) Specialized Center of Research (SCOR) program.