Myeloma Genome Project
The Myeloma Genome Project is a landmark global initiative compiling the largest set of molecular profiling data with associated clinical outcomes data to develop a segmentation strategy that identifies specific molecular classifications of multiple myeloma. The initiative eventually seeks to develop clinically relevant tests for genetic mutations that could improve the diagnosis, prognosis, and treatment of patients with multiple myeloma around the globe.
The Myeloma Genome Project has since begun integrating data sets collected not only from the UAMS Myeloma Center, but also from the Myeloma XI trial (UK), Intergroupe Francophone du Myeloma/Dana-Farber Cancer Institute, and the Multiple Myeloma Research Foundation. Researchers are using this large set of diverse genomic data to identify genetic information that may identify clinical targets for therapy.
The Myeloma Genome Project intends to build a global network through expanded collaboration with myeloma centers around the world.
Discovery of New Genetic Risk Factors for Myeloma: A UAMS Myeloma Center and European Collaboration
Genome-wide association study identifies multiple susceptibility loci for multiple myeloma. Researchers from the UK, Germany, the Netherlands, Sweden, and Iceland have identified eight new genetic variations in the human genome that could be linked to an increased risk of developing myeloma. The findings provide additional evidence and build on existing research that suggests myeloma can run in families.
As part of an international collaboration, the Myeloma Center team investigated whether the cause for this increase may be found in the germline DNA of patients. They analyzed characteristic changes in the genome of 9,866 patients and 239,188 healthy controls to identify inherited genetic variants that are seen more often in multiple myeloma patients. Methodologically, they conducted a meta-analysis of genome-wide association studies (GWASs) and investigated variations of single base pairs, so-called single nucleotide polymorphisms (SNPs).
This is the largest genome-wide association to date, and it identified new risk loci that have relevance to myeloma biology. The meta-analysis was based on GWAS conducted in the Netherlands, the United Kingdom, Germany, Sweden/Norway, the United States and Iceland.
Further studies are needed to understand the biology behind the risk variants. These studies, conducted in coordination with analyses of patients’ functional outcomes, are expected to lead to additional insights into myeloma biology that support the development of new therapeutic agents and personalized medicine approaches to treatment.
Genetic Factors Influencing the risk of multiple myeloma bone disease
Four cohorts of multiple myeloma patients were studied from previous genome-wide association studies comprising cases from the Myeloma Center, the UK Medical Research Council’s Myeloma IX-trial, and the German Myeloma Multicentre Group in Heidelberg. The findings report that an individual’s risk of developing bone disease is influenced by germline variation, specifically the identification of a locus at 8q24.12, thus providing the first evidence that germline variation influences not only a myeloma patient’s risk of developing bone disease but also importantly impacts it throughout disease progression.
These findings will contribute to the development of future strategies for the prevention of MBD in the early precancerous phases of myeloma.
The Perelman Family Foundation of Early Disease Translational Research Program
The Perelman Family Foundation of Early Disease Translational Research Program is the first research program dedicated to the early detection and prevention of multiple myeloma.
Established as part of the Multiple Myeloma Research Foundation (MMRF) Prevention Project to speed the efforts toward early detection, delayed disease progression, and ultimately, prevention of multiple myeloma, the $4 million program will focus on understanding genomic determinants of early myeloma progression, identifying microenvironment factors that influence early disease progression, and finding ways to strengthen immunity against the tumors.
Six leading myeloma research centers, including the UAMS Myeloma Center, will collaborate to identify novel targets and biomarkers of disease progression and enable the development of therapeutic approaches to delay or even stop progression to myeloma.
– Better understanding of genomic determinants of early disease progression
– Impact of microenvironmental factors on early disease progression
– Enhancing tumor immunity in MGUS/SMM
International Myeloma Working Group (IMWG): Collaboration and Consensus in the Search for a Cure
The mission of the IMWG is to conduct basic, clinical and translational research in a collaborative manner to improve outcomes in myeloma, and to provide scientifically valid and critically appraised consensus opinions on the diagnosis and treatment of myeloma and related disorders. The work focuses on the protocols to provide a more durable remission for myeloma patients while improving quality of life, and addressing the needs of both myeloma patients and the physicians who treat them. The collaboration has brought about breakthroughs in treatment options and diagnostics resulting in numerous publications.
Building Bones: Center for Integrative Nanotechnology Sciences (CINS) at UA Little Rock
The Myeloma Center is partnering with UA Little Rock’s Center for Integrative Nanotechnology Sciences in testing a new technology that builds new bone scaffolds for damaged bone that can encourage new bone formation. Myeloma is an ideal system in which to test this approach because of the destructive bone lesions which are so typical of this condition.
This technology, the NuCress™ scaffold, is a nanomaterial-based bone regeneration device pioneered by UA Little Rock’s Dr. Alexandru S. Biris, a systems engineering professor, Roy and Christine Sturgis Charitable Trust Nanotechnology chair, and director of the Center for Integrative Nanotechnology Sciences. Biris’s long-time research partner, Dr. David Anderson, a professor at the University of Tennessee College of Veterinary Medicine (UTCVM). Together, Biris, Anderson, and their teams have designed, patented, and tested the NuCress™ scaffold.
The scaffold is implanted directly by a surgeon and can be loaded with drugs to fight infection or with hormones and stem cells to encourage bone growth. As a result, the scaffold can deliver bacteria-fighting drugs directly to the wound site and be safely absorbed by the body—generally eliminating the need for additional surgeries.
NuShores Biosciences, LLC—the company commercializing the device—is preparing to apply to the U.S. Food and Drug Administration for regulatory approval of the scaffold, moving it one step closer to human use. The NuCress™ scaffold could become an essential part of the bone-healing process for injury victims, cancer survivors, and more.
Clinical trials link research and patient treatment by evaluating new drugs, therapies, and diagnostic tools to drive innovation into clinical practice. The Myeloma Center partners with industry and university to conduct a portfolio of clinical trials to bring to advance novel treatments and diagnostic approaches for patients with multiple myeloma and related diseases.
Clinical Trials at the Myeloma Center