IDIBAPS Researchers Discover Genetic Drivers of Clonal Evolution in Leukemia Using Single-Cell DNA Sequencing from Mission Bio

Mission Bio, the pioneer in high-throughput single-cell DNA and multi-omics analysis, announced new findings from the lab of Elías Campo, Director of the August Pi i Sunyer Biomedical Research Institute (IDIBAPS) in Barcelona, Spain, which used single-cell DNA sequencing to identify genetic drivers of Richter’s syndrome, the unpredictable and often deadly progression from chronic lymphocytic leukemia (CLL) to an aggressive B cell lymphoma. The study, published today in the journal Nature Medicine, was the latest to demonstrate clinically relevant insights using Mission Bio’s Tapestri® Platform, highlighting rare Richter’s Syndrome subclones that lie dormant for years and could be targeted therapeutically to prevent disease progression by uncovering mutations at the individual cell level.

There are about 20,000 patients diagnosed with CLL in the U.S. each year. Though CLL is often treatable, Richter’s syndrome can develop after treatment with targeted therapies, affecting up to 10% of patients and transforming the cancer into the more aggressive diffuse large B cell lymphoma (DLBCL), which has a median survival of one year or less.

In the new publication, the IDIBAPS-led team performed genomic, epigenomic, and transcriptomic characterization of CLL patients before and after treatment in an effort to understand drivers of Richter’s syndrome. By using Mission Bio’s highly sensitive Tapestri® CLL panel, the researchers were able to resolve clonal heterogeneity and trace the cancer’s evolutionary history, detecting rare pre-existing mutations associated with disease progression in samples from four patients. The results suggest that treatment was driving selection for subclones – an analysis that was not possible with traditional bulk sequencing methods that are incapable of detecting mutations that co-occur in the same cells.

The genomic drivers were identified in an extremely small number of subclones – about five cells – and detected years before final expansion. The findings could enable researchers to develop strategies targeting these dormant subclones to prevent CLL patients from developing Richter’s syndrome.

“Single-cell DNA sequencing, powered by Tapestri®, allowed us to resolve the co-mutational relationships within cells and unambiguously detect rare subclones at early stages of evolution that bulk sequencing missed,” said Ferran Nadeu, PhD, a postdoctoral researcher at IDIBAPS and the publication’s primary author.

“This is the latest example of how Tapestri® Platform empowers scientists to find drivers of cancer progression early in the course of disease, which could enable the development of predictive biomarkers and earlier therapeutic interventions,” said Todd Druley, M.D., PhD, Chief Medical Officer of Mission Bio. “This research makes a strong argument that single-cell DNA sequencing is a necessary tool to uncover mechanistic insight into cancer biology, enabling the development of diagnostics and therapeutics to fight this disease.”