Deciphering the molecular landscape in chronic lymphocytic leukemia: clinical and biological impact

Chronic lymphocytic leukemia (CLL), the most common leukemia among adults, is known for being highly heterogeneous in terms of clinical manifestation and outcome.

Taking advantage of our large, well-annotated cohort of CLL patients, we will apply a range of high-throughput technologies, including next-generation sequencing and single-cell technology, to investigate clinically relevant patient subgroups and follow their disease evolution.

By undertaking integrative analyses, we aim to map patient-specific pathogenic variants in the genome, transcriptome, and methylome, thus gaining detailed insight into the spectrum of molecular events occurring in patients belonging to clinically aggressive subgroups.

In addition, we will apply novel proteomic/proteogenomic approaches to link findings to dysregulated signalling pathways and other regulatory processes in CLL.

This newly acquired knowledge will be funneled into discovering novel drugs for targeted therapy using a high-throughput drug sensitivity screening approach.

The availability of longitudinal CLL samples provides us with a unique opportunity to determine whether genetic/epigenetic changes occur over time and will assist in identifying factors that influence treatment resistance.

Ultimately, this comprehensive molecular characterization will lead to significantly improved risk stratification in CLL, and the identification of new predictive biomarkers and treatment strategies in this as yet incurable disease.