Venetoclax inhibits the pro-survival protein BCL2 to induce apoptosis and is now standard therapy for chronic lymphocytic leukemia (CLL), delivering high complete remission rates and prolonged progression-free survival for patients with CLL who had been previously treated with chemotherapy. However, eventual relapse on venetoclax due to acquired resistance remains a major problem.

In this session, Dr Thijssen summarises the unappreciated scale of genetic and epigenetic changes underpinning acquired venetoclax resistance in CLL. Her findings pinpoint new approaches to circumvent venetoclax resistance. She provides specific biological justification for the strategy of venetoclax discontinuation once maximal response is achieved rather than maintaining long-term selective pressure with continuous venetoclax treatment.

Presenters

Dr Rachel Thijssen
Senior Postdoctoral Fellow
The Walter and Eliza Hall Institute of Medical Research

Dr Rachel Thijssen completed her PhD within the Immuno-Hematology department of the Academic Medical Center (AMC), Amsterdam, the Netherlands. Dr Thijssen is an emerging leader in the field of translational cancer research, with expertise in targeted therapies and single-cell technologies. With the support of a Leukemia & Lymphoma Society Fellowship, Victorian Cancer Agency Fellowship, Cure Cancer Grant and Leukaemia Foundation Grant, her research focuses on unravelling how haematopoietic cancer cells evade cell death, with a focus on venetoclax relapse in leukaemias using state-of-the-art single-cell technologies such as single-cell RNA-seq (CITE-seq) and single-cell long-read sequencing (Nanopore).