BC CLL/SLL Cohort

Project aims/goals
To define the molecular and cellular mechanisms driving resistance to novel therapies in chronic lymphocytic leukemia (CLL) and small lymphocytic lymphoma (SLL) through integrative whole genome, transcriptome, and single-cell sequencing of a clinically annotated patient cohort.
Summary
CLL/SLL is a blood cancer that has benefited from advances in targeted and immune based therapies, including BTK inhibitors, BCL2 inhibitors, and bispecific antibodies. However, many patients eventually relapse or develop resistance, and the underlying mechanisms are not fully understood. In this project, we will study a cohort of CLL/SLL patients treated with these novel therapies, using samples collected before treatment and at the time of relapse. By applying whole genome sequencing, RNA sequencing, and single-cell analysis, we aim to identify genetic and molecular changes that drive treatment resistance. Integrating these findings with longitudinal clinical data will help uncover biomarkers of resistance, improve our understanding of clonal evolution, and support the development of more effective and personalized treatment strategies for patients with CLL/SLL.
Anticipated outcomes and impact
Through this project, we expect to better understand why some CLL/SLL patients stop responding to novel targeted and immune based treatments. By analyzing genetic and molecular changes in leukemia cells before and after treatment, we aim to identify patterns that may explain how the disease becomes resistant. Using advanced techniques like single-cell sequencing, we will also study how individual leukemia cells evolve and how the immune system interacts with the cancer over time. This work will help identify potential markers of resistance and new treatment targets. Ultimately, our goal is to improve how we predict, prevent, and manage treatment resistance, leading to more personalized and effective care for people living with CLL and SLL.
Key Researchers
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Alina
Research Lead
Gerrie -
Christian
ResearcherMOHCCN Network CouncilWorking Group Chair
Steidl -
David
Project LeaderWorking Group Member
Scott