Immune system changes occur early in development of multiple myeloma, study finds

April 27, 2020

Long before multiple myeloma becomes a malignant disease, the collection of immune system cells and signal carriers amid the tumor cells undergoes dramatic shifts, with alterations in both the number and type of immune cells, researchers at Dana-Farber Cancer Institute, the Broad Institute of MIT and Harvard, and Massachusetts General Hospital (MGH) report in a new study.

The findings, published online today by the journal Nature Cancer, are a step toward more personalized treatment of multiple myeloma. Future treatments may be geared to the immune microenvironment of each patient's disease - the specific constellation of immune cells in and around myeloma tissue - the study authors say.

"Our results provide a comprehensive map of the immune changes that take place in pre-malignant myeloma," said Irene Ghobrial, MD, of Dana-Farber, the Broad Institute, the co-senior author of the study with Gad Getz, PhD, of the Broad Institute and MGH. "The discovery that the immune microenvironment is abnormal even at very early stages of the disease may suggest strategies for targeting myeloma before it becomes malignant."

Multiple myeloma is a cancer of white blood cells known as plasma cells in the bone marrow. It is preceded by precursor conditions known as monoclonal gammopathy of unknown significance (MGUS) and smoldering multiple myeloma (SMM), in which people have abnormal plasma cells in their bone marrow but no physical symptoms or organ problems. Because not everyone with MGUS or SMM develops outright myeloma, treatment doesn't begin until symptoms of myeloma - such as bone pain, low blood counts, kidney problems, and nerve damage - appear. Researchers are working on ways to intercede in the disease process early on to identify individuals at risk and prevent the development of full-blown myeloma.

The new study represents the first time that single-cell RNA sequencing - in which scientists pluck individual cells from tissue and scan their RNA to determine which genes are active - has been used to identify features of the immune microenvironment in myeloma precursor conditions.

"We wanted to understand the changes that occur in the microenvironment as the disease progresses from MGUS to SMM to overt myeloma, as compared to the bone marrow of healthy tissue donors," said co-first author Oksana Zavidij, PhD, of Dana-Farber and the Broad Institute. "The approach could ultimately shed light on why some patients progress to myeloma while others don't and help us better target treatments to individual patients."

The analysis revealed major immune changes early in the course of myeloma development:"These changes didn't correspond to any particular precursor condition," said co-first author Nicholas Haradhvala, of the Broad Institute, MGH, and the Harvard Graduate Program in Biophysics. "They were found in different combinations in patients with MGUS and SMM, suggesting an axis upon which patients could be stratified for evaluation of individual-specific risk of progression and potential for early intervention."

"Our findings have described the landscape of dysregulated immune system that can be used to follow up in much larger studies and build robust associations with patient risk and progression," added Getz.
The co-lead author of the study with Zavidij and Haradhvala is Tarek Mouhieddine, MD, of Dana-Farber and the Broad Institute. The co-senior author with Ghobrial and Getz is Jamil Azzi, MD, of Dana-Farber and Brigham and Women's Hospital (BWH). Co-authors are Romanos Sklavenitis-Pistofidis, MD, Mairead Reidy, PhD, Mahshid Rahmat, PhD, Michael P. Agius, PhD, Jihye Park, PhD, Mark Bustoros, MD, Marzia Capelletti, PhD, and Eliezer van Allen, MD, of Dana-Farber and the Broad Institute; Songjie Cai, MD, PhD, Abdallah Flaifel, MD, and Benjamin Ferland, of BWH; Nang K. Su, Salomon Manier, MD, Daisy Huynh, Brianna Berrios, Chia-Jen Liu, MD, PhD, and Jennifer L. Guerriero, PhD, of Dana-Farber; Meng Xiao He of the Broad Institute and the Harvard Graduate Program in Biophysics; Esteban Braggio, PhD, and Rafael Fonseca, MD, of the Mayo Clinic Arizona; and Yosef Maruvka, PhD, Melissa Goldman, Steven A. McCarroll, PhD, of the Broad Institute.

Funding for the study was provided by the National Institutes of Health grant (grants NIH R01 CA 205954 and R01CA181683); the Leukemia and Lymphoma Society; Multiple Myeloma Research Foundation; the Adelson Medical Research Foundation; and Stand Up to Cancer.

Dana-Farber Cancer Institute

Related Science Articles from Brightsurf:

75 science societies urge the education department to base Title IX sexual harassment regulations on evidence and science
The American Educational Research Association (AERA) and the American Association for the Advancement of Science (AAAS) today led 75 scientific societies in submitting comments on the US Department of Education's proposed changes to Title IX regulations.

Science/Science Careers' survey ranks top biotech, biopharma, and pharma employers
The Science and Science Careers' 2018 annual Top Employers Survey polled employees in the biotechnology, biopharmaceutical, pharmaceutical, and related industries to determine the 20 best employers in these industries as well as their driving characteristics.

Science in the palm of your hand: How citizen science transforms passive learners
Citizen science projects can engage even children who previously were not interested in science.

Applied science may yield more translational research publications than basic science
While translational research can happen at any stage of the research process, a recent investigation of behavioral and social science research awards granted by the NIH between 2008 and 2014 revealed that applied science yielded a higher volume of translational research publications than basic science, according to a study published May 9, 2018 in the open-access journal PLOS ONE by Xueying Han from the Science and Technology Policy Institute, USA, and colleagues.

Prominent academics, including Salk's Thomas Albright, call for more science in forensic science
Six scientists who recently served on the National Commission on Forensic Science are calling on the scientific community at large to advocate for increased research and financial support of forensic science as well as the introduction of empirical testing requirements to ensure the validity of outcomes.

World Science Forum 2017 Jordan issues Science for Peace Declaration
On behalf of the coordinating organizations responsible for delivering the World Science Forum Jordan, the concluding Science for Peace Declaration issued at the Dead Sea represents a global call for action to science and society to build a future that promises greater equality, security and opportunity for all, and in which science plays an increasingly prominent role as an enabler of fair and sustainable development.

PETA science group promotes animal-free science at society of toxicology conference
The PETA International Science Consortium Ltd. is presenting two posters on animal-free methods for testing inhalation toxicity at the 56th annual Society of Toxicology (SOT) meeting March 12 to 16, 2017, in Baltimore, Maryland.

Citizen Science in the Digital Age: Rhetoric, Science and Public Engagement
James Wynn's timely investigation highlights scientific studies grounded in publicly gathered data and probes the rhetoric these studies employ.

Science/Science Careers' survey ranks top biotech, pharma, and biopharma employers
The Science and Science Careers' 2016 annual Top Employers Survey polled employees in the biotechnology, biopharmaceutical, pharmaceutical, and related industries to determine the 20 best employers in these industries as well as their driving characteristics.

Three natural science professors win TJ Park Science Fellowship
Professor Jung-Min Kee (Department of Chemistry, UNIST), Professor Kyudong Choi (Department of Mathematical Sciences, UNIST), and Professor Kwanpyo Kim (Department of Physics, UNIST) are the recipients of the Cheong-Am (TJ Park) Science Fellowship of the year 2016.

Read More: Science News and Science Current Events is a participant in the Amazon Services LLC Associates Program, an affiliate advertising program designed to provide a means for sites to earn advertising fees by advertising and linking to