Earlier this year, Dr. Robert Bowman, Assistant Professor of Cancer Biology at the University of Pennsylvania, presented a webinar where he discussed how single-cell analysis can be leveraged to study clonal evolution and myeloid malignancies, focusing on how mutations cause clonal expansion in cancer.
Understanding Somatic Evolution in Cancers
In his presentation, Dr. Bowman highlighted the role of somatic evolution in various cancers, particularly clonal hematopoiesis in peripheral blood as an early form of somatic mosaicism, which is common in people over 60 and often involves DNMT3A and TET2 mutations linked to DNA methylation changes. Although acute myeloid leukemia (AML) is a rare outcome of clonal hematopoiesis, specific mutation combinations can lead to poor prognosis.
Researchers aim to understand why clonal hematopoiesis frequently occurs while leukemia remains rare by using innovative research technology, such as single-cell DNA sequencing with the Tapestri Platform and CRISPR Cas9 editing.
Leveraging Disease Modeling in Mice
Dr. Bowman’s research illustrated how mouse model experiments can be leveraged to study AML development through sequential genetic mutations like IDH2, FLT3, and DNMT3A, demonstrating that even a small percentage of mutated cells can initiate AML. Single-cell DNA sequencing and protein data analysis were employed to identify mutation types and their impact on cell behavior and disease progression. Additionally, examining cell clusters based on markers like CD14, CD11b, and CD64 can be key to understanding the relationship between cell genotype and characteristics.
“We’re able to take human samples like the ones I’ve shown you, look to see which cells are actually mutated in those human samples and make hypotheses about potential cells of origin in mice. And we can do this loop where we set up models of mice to learn about the human system, characterize the human clinical specimen, and use that to drive hypotheses in mice to ask questions that are important for disease biology. I think the future of these assays really is in multi-omic assays.” – Dr. Robert Bowman
The Importance of Building Disease Models that can Recapitulate Human Disease
Integrating tools like CRISPR Cas9 and single-cell DNA sequencing with Tapestri aid in modeling disease patterns and clonal evolution in both patient populations and mouse models. When looking to the future of disease modeling, Dr. Bowman emphasized how critical including multi-omic assays for comprehensive cell information will be, as well as integrating DNA methylation studies, and developing analytical tools for data interpretation.
You can watch Dr. Bowman’s full presentation here.
