Mount Sinai Researchers Help Create Largest Immune Cell Atlas of Bone Marrow in Multiple Myeloma Patients

Mount Sinai Researchers Help Create Largest Immune Cell Atlas of Bone Marrow in Multiple Myeloma Patients

Scientists at the Icahn School of Medicine at Mount Sinai, in partnership with the Multiple Myeloma Research Foundation (MMRF) and in collaboration with leading institutions across the country, have helped generate the largest single-cell immune cell atlas of the bone marrow in patients with multiple myeloma, a blood cancer that, while treatable, remains incurable. The findings, published in Nature Cancer, provide unprecedented insight on immune dysfunction in myeloma and could lead to improved tools for predicting which patients are at higher risk of relapse after treatment.

The study analyzed nearly 1.5 million immune cells from the bone marrow of 335 newly diagnosed patients in the MMRF's CoMMpass study dataset, using a cutting-edge technique called single-cell RNA sequencing. This approach allowed researchers to examine the molecular features of individual cells, revealing previously hidden patterns in how the immune system behaves in the presence of multiple myeloma.

"Currently, doctors rely heavily on the genetic features of cancer cells to estimate how aggressive their disease is," said co-senior author Sacha Gnjatic, PhD, Professor of Immunology and Immunotherapy at the Mount Sinai Tisch Cancer Center. "Our research shows that the immune cells surrounding the tumor are just as important in determining how the disease progresses, and this could lead to earlier, more targeted treatment strategies."

"The scale and maturity of the MMRF's CoMMpass study and the breadth of this multi-center collaboration highlights the importance of creating 'big science' teams," added George Mulligan, PhD, co-senior author and Chief Scientific Officer at the MMRF.

The team discovered that some patients who relapsed quickly after initial therapy had distinct immune cell populations in their bone marrow at the time of diagnosis. Notably, a subset of T cells (immune cells typically responsible for attacking tumors) appeared to show a state of immunosenescence, meaning they were present but not functioning effectively and contributing to immune suppression. In addition, the study uncovered patterns of communication between immune cells and cancer cells that may support tumor growth.

These insights suggest that the immune system's response to myeloma could be used as a predictive tool, offering a complementary layer to traditional genetic testing. While the current technology used in the study is primarily for research, the investigators hope the findings will inform the development of simple, broadly available tests in the future.

"This work not only provides new biological insights, but also lays the groundwork for future discoveries," Dr. Gnjatic said. "It could help researchers around the world better understand how the immune system interacts with cancer and ultimately, help improve outcomes for patients."

The MMRF designed and funded this collaborative research, which involved equal contribution from scientists at Mount Sinai, Emory University, Beth Israel Deaconess Medical Center, Washington University in St. Louis's Siteman Cancer Center, the Mayo Clinic, and the MMRF. Mount Sinai's Edgar Gonzalez-Kozlova, PhD, was co-first author along with other lead data analysts from the six institutions, while other important contributors from Mount Sinai included Seunghee Kim-Schulze, PhD, the lead for data generation, and Hearn J. Cho, MD/PhD, a Mount Sinai myeloma oncologist and researcher who is also Chief Medical Officer at the MMRF.

The large patient sample size and robust clinical annotations-enabled by the MMRF's extensive biorepository and 12 years of patient data-make this one of the most comprehensive resources of its kind. This report will significantly contribute to our understanding of immune function in multiple myeloma.

About the Icahn School of Medicine at Mount Sinai

The Icahn School of Medicine at Mount Sinai is internationally renowned for its outstanding research, educational, and clinical care programs. It is the sole academic partner for the seven member hospitals* of the Mount Sinai Health System, one of the largest academic health systems in the United States, providing care to New York City's large and diverse patient population. 

The Icahn School of Medicine at Mount Sinai offers highly competitive MD, PhD, MD-PhD, and master's degree programs, with enrollment of more than 1,200 students. It has the largest graduate medical education program in the country, with more than 2,600 clinical residents and fellows training throughout the Health System. Its Graduate School of Biomedical Sciences offers 13 degree-granting programs, conducts innovative basic and translational research, and trains more than 560 postdoctoral research fellows. 

Ranked 11th nationwide in National Institutes of Health (NIH) funding, the Icahn School of Medicine at Mount Sinai is among the 99th percentile in research dollars per investigator according to the Association of American Medical Colleges.  More than 4,500 scientists, educators, and clinicians work within and across dozens of academic departments and multidisciplinary institutes with an emphasis on translational research and therapeutics. Through Mount Sinai Innovation Partners (MSIP), the Health System facilitates the real-world application and commercialization of medical breakthroughs made at Mount Sinai.

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* Mount Sinai Health System member hospitals: The Mount Sinai Hospital; Mount Sinai Brooklyn; Mount Sinai Morningside; Mount Sinai Queens; Mount Sinai South Nassau; Mount Sinai West; and New York Eye and Ear Infirmary of Mount Sinai.

About the Mount Sinai Health System

Mount Sinai Health System is one of the largest academic medical systems in the New York metro area, with 48,000 employees working across seven hospitals, more than 400 outpatient practices, more than 600 research and clinical labs, a school of nursing, and a leading school of medicine and graduate education. Mount Sinai advances health for all people, everywhere, by taking on the most complex health care challenges of our time-discovering and applying new scientific learning and knowledge; developing safer, more effective treatments; educating the next generation of medical leaders and innovators; and supporting local communities by delivering high-quality care to all who need it.

Through the integration of its hospitals, labs, and schools, Mount Sinai offers comprehensive health care solutions from birth through geriatrics, leveraging innovative approaches such as artificial intelligence and informatics while keeping patients' medical and emotional needs at the center of all treatment. The Health System includes approximately 9,000 primary and specialty care physicians and 10 free-standing joint-venture centers throughout the five boroughs of New York City, Westchester, Long Island, and Florida. Hospitals within the System are consistently ranked by Newsweek's^® "The World's Best Smart Hospitals, Best in State Hospitals, World Best Hospitals and Best Specialty Hospitals" and by U.S. News & World Report's^® "Best Hospitals" and "Best Children's Hospitals." The Mount Sinai Hospital is on the U.S. News & World Report^® "Best Hospitals" Honor Roll for 2025-2026.

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