Single-Cell DNA Sequencing 2022 - Using Single-Cell DNA Sequencing to Unravel Clonal Heterogeneity & Progression to Richter’s Transformation in CLL

Richter’s transformation (RT) is a rare condition in patients with chronic lymphocytic leukemia (CLL) which transforms into a much more aggressive form of B cell lymphoma, conferring a poor prognosis. The mechanisms and molecular changes that drive RT remain largely unknown. In this webinar, the featured speaker, Dr. Ferran Nadeu, will discuss their research study recently published in Nature Medicine where they applied single-cell DNA sequencing (scDNA-seq) to resolve clonal heterogeneity and detect rare pre-existing mutations associated with disease transformation. To identify the genetic driver mutations and evolutionary histories over the disease course, Dr. Nadeu’s lab first sequenced the whole genome of 54 longitudinal samples covering up to 19 years of disease course in 19 cases of CLL developing RT. They then performed single-cell DNA sequencing using the Tapestri Platform and the 32-gene CLL Catalog Panel from Mission Bio on 16 longitudinal samples of four cases to validate these evolutionary histories of RT, and to track early driver mutations over the disease course. The speaker will discuss how single-cell DNA sequencing allowed high-sensitivity detection of driver mutations that bulk next-generation sequencing didn’t call, identifying minute subclones at the time of CLL diagnosis which were dormant for six to 19 years until rapid expansion at transformation. He will also overview the findings from the study that suggest that CLL evolution to RT is driven by pre-existing subclones generated before diagnosis and that early intervention to eradicate the dormant RT subclones may prevent the future development of this lethal complication of CLL, uncovering potential therapeutic targets for RT. Register to learn about unraveling clonal heterogeneity & progression to Richter’s transformation in chronic lymphocytic leukemia with single-cell DNA sequencing.