This webinar, the second of the “Women in Single Cell” series, discusses 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 discusses 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 also discusses 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.