This webinar, the second of the “Women in Single Cell” series, will discuss the use of single-cell technologies to investigate clonal architecture and genotype/immunophenotype relationships in myeloid malignancies.
Acute myeloid leukemia (AML) derives from genetic and epigenetic events that lead to abnormal clonal expansion and evolution of hematopoietic stem/progenitor cells (HSPCs). Bulk genomic sequencing studies in AML patients suggest that stepwise acquisition of somatic mutations is critical in driving AML development, progression, and maintenance. However, bulk sequencing is unable to delineate co-occurring mutations at a clonal level or clearly elucidate mutation order.
Dr. Linde A. Miles will discuss her recent publication in Nature in which she and colleagues performed single-cell DNA sequencing on samples from patients with myeloid malignancies, including AML patients. They used a custom panel spanning the 31 most frequently mutated AML genes with the Mission Bio Tapestri single-cell sequencing platform. The team identified gene-specific patterns within the dominant clones and uncovered synergistic co-mutations in AML capable of promoting clonal dominance and expansion. They also combined single-cell mutational analysis with cell surface protein expression to map clonal architecture and genotype/immunophenotype relationships.
Dr. Miles will also discuss newer studies using single-cell multi-omics that focus on the correlations between co-occurring mutations and immunophenotype. Findings from these studies provide a better understanding of clonal evolution in leukemic transformation and progression.
Dr. Linde Miles graduated from Pennsylvania State University in 2009 and received her Ph.D. in Pharmacology & Molecular Sciences from Johns Hopkins University School of Medicine in 2016. Dr. Miles is currently a Marie-Josée Kravis Women in Science Endeavour (WiSE) postdoctoral fellow at Memorial Sloan Kettering Cancer Center in the lab of Dr. Ross Levine. Her research focuses on clonal evolution in AML and the impact of mutation order in leukemogenesis.
