The Chronic Lymphocytic Leukemia Channel on VJHemOnc is an independent medical education platform, supported with funding from AstraZeneca (Diamond), AbbVie (Platinum), BeOne Medicines (Silver) and Lilly (Silver). Supporters have no influence on the production of content. The levels of sponsorship listed are reflective of the amount of funding given.
EHA 2025 | Identifying and targeting survival co-dependencies of CLL resistant to venetoclax
As the number of patients with chronic lymphocytic leukemia (CLL) receiving targeted therapies increases, a greater number of patients are becoming refractory to BTK and BCL2 inhibitors. In this video, Daisy Diaz Rohena, PhD, and Deepa Sampath, PhD, from The University of Texas MD Anderson Cancer Center, Houston, TX, discuss their work aimed at understanding and targeting transcriptional reprogramming and survival co-dependencies in CLL resistant to venetoclax. Having identified BCL2 and Bcl-xL as proteins that confer co-dependency in CLL, Dr Sampath and her team targeted these proteins with a novel proteolysis-targeting chimera (PROTAC) degrader, observing promising results in preclinical studies. This interview took place at the 30th Congress of the European Hematology Association (EHA) in Milan, Italy.
These works are owned by Magdalen Medical Publishing (MMP) and are protected by copyright laws and treaties around the world. All rights are reserved.
Transcript
Deepa:
CLL has a lot of options but now with more and more patients on targeted therapy like the BTKi and the BCL2 inhibitors many patients become refractory and their options are very poor. So at MD Anderson my group and Daisy is my student who did all this work during her PhD has come up with new options for dual refractory CLL...
Deepa:
CLL has a lot of options but now with more and more patients on targeted therapy like the BTKi and the BCL2 inhibitors many patients become refractory and their options are very poor. So at MD Anderson my group and Daisy is my student who did all this work during her PhD has come up with new options for dual refractory CLL. Would you like to say something more about it, Daisy?
Daisy:
Yes, we have integrated single cell RNA sequencing data, as well as using BH3 profiling, a precision medicine technique that allows us to understand on which anti-apoptotic proteins do CLL cells depend on to survive. And we have pinpointed BCL2 and BCLXL as two proteins that grant codependency in CLL. We are now targeting these proteins with a PROTAC degrader. This is a novel way to degrade BCLXL and in a way that circumvents on-target toxicity to platelets, which is important for patient safety. And we have completed preclinical work on this study in patient samples, refractory to venetoclax, or that relapse to venetoclax and ibrutinib, including BTK mutant samples and BCL2 mutant samples with great results. And we hope to complete these studies and continue it to animal testing.
Deepa:
We also hope to start a clinical trial early next year, either with this compound or the next generation compound. And we’re looking forward to those results.
This transcript is AI-generated. While we strive for accuracy, please verify this copy with the video.
Read more...
