New study led by University Cancer Center of Toulouse shows high frequency of RAS/RAF subclone mutations in MM
Mission Bio, a leader in single-cell multi-omics solutions for precision medicine, announced a new publication led by Hervé Avet-Loiseau, MD, PhD, revealing new insights into disease progression of multiple myeloma (MM). Using Mission Bio’s single-cell DNA sequencing Tapestri® Platform, the study shows that solely targeting the RAS/RAF pathway for therapeutic intervention or residual disease assessment for MM may not be a viable approach due to the oligoclonal progression of the disease. More specifically, Tapestri demonstrated that variable subclonal RAS/RAF mutations occur disparately, highlighting the ongoing nature of subclonal evolution in MM and suggesting that only targeting and tracking RAS/RAF mutations is insufficient to expect a curative result.
MM is a blood cancer that develops in bone marrow plasma cells and often requires an iterative treatment strategy to prolong patient survival. One approach that researchers and biopharma companies use for therapeutic selection and residual disease surveillance is targeting RAS/RAF mutations, which occur in about 50% of MM patients. The problem is that disease progression occurs through branching patterns of clonal evolution with the emergence of multiple subclones that already exist at early precancerous stages and have different constellations of mutations than the primary MM clone seen by bulk measures at the time of diagnosis. These low-frequency subclones can outcompete other clones due to the selective pressure of the therapeutic agents prescribed. This clonal evolution drives an ever-changing MM heterogeneity, making therapy selection challenging.
In the article, “RAS/RAF landscape in monoclonal plasma cell conditions” published in Blood, Avet-Loiseau’s team retrospectively explored RAS/RAF mutations in a large cohort (>10,000) of patients with plasma cell disorders. The scientists discovered that a majority of the patients had a RAS/RAF mutation at diagnosis or relapse, which was not as evident in pre-symptomatic cases and different in solid tumors. In a subset of samples, the researchers used Tapestri for single-cell DNA sequencing to evaluate co-occurring KRAS/NRAS or BRAF V600E mutations, which revealed the high-frequency subclonal nature of RAS/RAF mutations in MM. Due to the ongoing subclonal mutational process found in MM, the data suggests that targeted therapies and monitoring disease progression against RAS/RAF are unlikely to be viable options.
Avet-Loiseau, Head of the Laboratory for Genomics in Myeloma, University Cancer Center of Toulouse, said, “Since MM is a heterogeneous malignancy, clinicians have been unable to provide patients with safe and effective therapies. Through Mission Bio’s technology, we’ve demonstrated that the mutational landscape of MM is continually evolving, providing new insights into the disease’s complexity. In the future, we hope to use this data to better inform treatment strategies for this hard-to-treat blood cancer.”
Adam Sciambi, PhD, co-founder and Chief Technology Officer of Mission Bio, commented, “At Mission Bio, our goal is to enable our customers to identify unique variabilities in cancer at the single-cell level that will drive improved understanding of disease biology, risk stratification, therapeutic selection, and surveillance. As demonstrated by our collaboration with Dr. Avet-Loiseau, we will continue to work closely with leading hematology and oncology researchers as we aim to continue demonstrating how subclonal understanding of the disease can potentially lead to improved patient outcomes in the future.”
About Mission Bio
Mission Bio is a leading life science company, specializing in the advancement of single-cell DNA and multi-omics analysis. The company’s Tapestri Platform is unique in its capabilities, offering an unparalleled level of granularity and precision that is critical for complex research areas such as cancer studies, pharmaceutical development, and advanced cell and gene therapies. Unlike traditional methods such as bulk sequencing, Tapestri provides a level of precision that opens the door for more tailored and effective treatment strategies. Researchers globally depend on Tapestri to identify rare cell populations, understand mechanisms of therapeutic resistance and response, and establish key quality metrics for next-generation medical treatments. Founded in 2014, Mission Bio has secured investment from firms including Mayfield Fund, Novo Growth, Cota Capital, and Agilent Technologies. With the Tapestri Platform, Mission Bio is setting the standard in the field, contributing significantly to the progress of personalized medicine and targeted therapies. To learn more about Mission Bio and the Tapestri Platform, please visit missionbio.com.
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