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.

Speakers

Ferran Nadeu, Postdoctoral Researcher, Institut d’Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), Barcelona, Spain

Ferran Nadeu, PhD graduated from the University of Barcelona in 2013 and went on to receive his MSc in bioinformatics for health sciences from Pompeu Fabra University in 2015, and PhD in biomedicine from the University of Barcelona in 2020. Dr. Nadeu is currently a postdoctoral researcher in the lab of Elías Campo, MD, PhD at the Institut d’Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS) in Barcelona, Spain. His research focuses on the molecular pathology of chronic lymphocytic leukemia (CLL) and lymphomas.

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Simone Formisano, Technical Application Liaison, Mission Bio

Simone Formisano is Technical Application Liaison at Mission Bio. He obtained his Master’s Degree in Biotechnology at Columbia University, New York City (United States). Before joining Mission Bio in 2022, Simone completed his Doctorate experimental work in cancer immunotherapy at Ludwig Maximilian University of Munich. Afterward, he contributed to the clinical development of several therapies in solid oncology by joining Daiichi Sankyo as a Medical Science Liaison.

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