One-size treatment for blood cancer probably doesn’t fit all, researchers say

Most multiple myeloma studies involve people of European descent, but the disease is more likely to affect African-Americans

PHOENIX and LOS ANGELES — Nov. 22, 2017 — Though African-American men are three times more likely to be diagnosed with a blood cancer called multiple myeloma, most scientific research on the disease has been based on people of European descent, according to a study published today in the scientific journal PLOS Genetics.

The study was led by researchers at the Keck School of Medicine of the University of Southern California (USC) and the Translational Genomics Research Institute (TGen).

The trend is problematic, considering that African-Americans — the most at-risk population for multiple myeloma — have different genetics that can affect how this type of cancer progresses and what kind of targeted therapies are most effective, said Dr. Zarko Manojlovic, Assistant Professor of Research Translational Genomics at the Keck School of Medicine, and lead author of the study.

For example, in the study, multiple myeloma patients of European descent were six times more likely than their African peers to have mutations in the TP53 gene, a tumor suppressor that helps prevent cancer. African-Americans, on the other hand, experienced heightened mutations in BCL7A, a different tumor suppressor gene.

“A cancer therapy that targets TP53 would not be as effective for African-Americans with multiple myeloma as it would be for a Caucasian population,” Dr. Manojlovic said.

Researchers analyzed the genetic sequencing data of 718 multiple myeloma patients and found that African-Americans had increased mutations in the genes BCL7A, BRWD3 and AUTS2, while Caucasians had more mutations in the genes TP53 and IRF4.

The study is the largest and most ethnically diverse genomics study of multiple myeloma to date, the researchers said.

“This study provides a unique view on the genetic differences of multiple myeloma in African-American and Caucasian populations that is only possible in studies like the MMRF (Multiple Myeloma Research Foundation) CoMMpass study, which was designed to collect a patient cohort reflective of the demographics of the United States population,” said Dr. Jonathan Keats, Director of Bioinformatics at TGen, and a co-author of the study.

The scientists genetically analyzed the ancestry for all patients and found that 127 patients were of African descent and 591 were of European descent.

“There are clearly molecular differences between African-American and Caucasian multiple myeloma cases, and it will be critical to pursue these observations to better improve clinical management of the disease for all patients,” said Dr. John D. Carpten, Chair of the Department of Translational Genomics at the Keck School of Medicine, and the study’s senior author.

Higher incidence; lower survival for African-Americans

Multiple myeloma is a cancer of plasma cells in the blood that causes tumor growths in bone marrow. More than 30,000 people will be diagnosed this year, and about half of them will survive longer than five years, according to the National Cancer Institute.

African-Americans are two times more likely than Caucasians to die from multiple myeloma, the study stated.

“In the past decade, new treatments for the disease have spurred a remarkable improvement in survival for myeloma patients, but those benefits have disproportionately increased survival rates for Caucasian patients,” Dr. Carpten said. “African-American multiple myeloma patients have higher incidence rates and lower survival rates than their Caucasian peers despite this being a relatively easy-to-treat cancer.

“We in the cancer genomics community have a responsibility to ensure that our studies represent true population diversity so we can understand the role of ancestry and biology in health outcomes. The new candidate myeloma genes we identified in the African-American population may have been overlooked because of the lack of diversity in previous genomic efforts.

“Also contributing to this study were: Dr. David W. Craig from the Keck School of Medicine; Dr. Winnie Liang, Jessica Aldrich, Austin Christofferson, Megan Washington and Shukmei Wong from TGen; Daniel Rohrer and Dr. Scott Jewell from the Van Andel Research Institute; and Dr. Rick Kittles and Mary Derome from the Multiple Myeloma Research Foundation.

Researchers used data from the Multiple Myeloma Research Foundation (MMRF) CoMMpass Study. The study — Comprehensive molecular profiling of 718 Multiple Myelomas Reveals Significant Differences in 4 Mutation Frequencies Between African and European Descent Cases — was supported by the USC Department of Translational Genomics and MMRF.


Translational Genomics Research Institute (TGen) is a Phoenix, Arizona-based non-profit organization dedicated to conducting groundbreaking research with life changing results. TGen is focused on helping patients with neurological disorders, cancer, diabetes, and infectious diseases, through cutting edge translational research (the process of rapidly moving research towards patient benefit). TGen physicians and scientists work to unravel the genetic components of both common and rare complex diseases in adults and children. Working with collaborators in the scientific and medical communities literally worldwide, TGen makes a substantial contribution to help our patients through efficiency and effectiveness of the translational process. TGen is affiliated with City of Hope, a world-renowned independent research and cancer and diabetes treatment center: This precision medicine affiliation enables both institutes to complement each other in research and patient care, with City of Hope providing a significant clinical setting to advance scientific discoveries made by TGen.

About the Keck School of Medicine of USC
Founded in 1885, the Keck School of Medicine of USC is among the nation’s leaders in innovative patient care, scientific discovery, education and community service. The school has approximately 1,650 full-time faculty members and voluntary faculty of more than 2,400 physicians. These faculty direct the education of approximately 800 medical students and 1,000 students pursuing graduate and postgraduate degrees. The school trains more than 900 resident physicians in more than 50 specialty or subspecialty programs and is the largest educator of physicians practicing in Southern California. Together, the school’s faculty and residents serve more than 1.5 million patients each year at Keck Hospital of USC and USC Norris Cancer Hospital, as well as USC-affiliated hospitals Children’s Hospital Los Angeles and Los Angeles County + USC Medical Center. Keck School faculty also conduct research and teach at several research centers and institutes, including the Zilkha Neurogenetic Institute and the Eli and Edythe Broad Center for Stem Cell Research and Regenerative Medicine at USC. In 2017, U.S. News & World Report ranked Keck School of Medicine among the top 35 medical schools in the country.

Steve Yozwiak
TGen Sr Science Writer

Zen Vuong
USC Health and Medical Research Writer

Posted in AZBio News.