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St. Jude Researchers Use Mission Bio's Single-Cell DNA Platform to Elucidate Genomic Landscape of Pediatric ALL

Friday, September 02, 2022

Mission Bio, a company specializing in high-throughput single-cell DNA and multi-omics analysis, has announced new research findings from St. Jude Children's Research Hospital and colleagues published in Nature Genetics. The researchers utilized Mission Bio's Tapestri® Platform to gain insights into how mutations at the single-cell level contribute to cancer relapse in pediatric acute lymphoblastic cancer (ALL). Understanding these mutations at a granular level is crucial for comprehending cancer development and determining personalized interventions for individual patients.

Pediatric acute lymphoblastic cancer (ALL) is the most common type of cancer in children, affecting the blood and bone marrow's white blood cells. If left untreated, excess immature white blood cells can crowd out normal white blood cells in the bone marrow, making it more challenging for the body to fight infections.

The study involved sequencing DNA from over 2,700 patients and transcriptomes from nearly 1,900 patients, led by teams from St. Jude and the Children's Hospital of Philadelphia. They identified several previously unknown pathways and genes affected by recurrent genomic alterations. By understanding mutation patterns associated with different disease subtypes, the origin and development of mutations (mutational ontogeny), the role of various mutational processes, and the nature of clonal evolution, the researchers demonstrated that many commonly targeted mutations in ALL can occur in different clones. These findings may contribute to the development of more personalized treatment approaches. The data also suggest that tracking patient mutations at the single-cell level during treatment could aid in monitoring disease recurrence.

This research showcases how Mission Bio's Tapestri® Platform enables researchers to examine intricate details of cancer biology at the single-cell level, which is not feasible with bulk sequencing methods. Single-cell sequencing allowed for the examination of co-occurring and mutually exclusive mutations, details that cannot be resolved through non-single-cell sequencing approaches. Such analyses are increasingly demanded by high-impact publications to gain insights into mutation presence and map the clonal evolution of cancer cells in diseases. This information is crucial for designing precision therapeutics, interventions, and understanding the drivers of treatment relapse in patients.

Dr. Charles Mullighan, Deputy Director of the Comprehensive Cancer Center at St. Jude's and co-leader of the hematological malignancies program, stated, "This type of analysis provides unique insight into clonal evolution and shows that kinase-related mutations, for example, are often secondary events and most frequently mutually exclusive. Simultaneous targeted single-cell DNA sequencing and cell-surface protein expression analysis reveal a correlation between immunophenotype and genotype within the same cell. This type of information is not only clinically relevant but potentially actionable and helps to fine-tune the expansive genomic landscape of pediatric ALL."

Todd Druley, Chief Medical Officer at Mission Bio, emphasized the significance of the Tapestri® Platform in delivering unprecedented single-cell information to oncologists. This information can guide personalized treatments for patients. The ability to identify and track targetable mutations in single cells offers a new dimension and specificity for clinicians seeking to detect residual or recurring cancer.

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