Evolution of Advanced Chronic Lymphoid Leukemia Unveiled by Single-Cell Transcriptomics: A Case Report

Area of Science:

• Hematology
• Genomics
• Immunology

Background:

• Chronic lymphocytic leukemia (CLL) exhibits genetic and transcriptional heterogeneity, complicating disease progression management.
• Longitudinal single-cell transcriptomics is crucial for profiling CLL heterogeneity and understanding disease evolution.

Observation:

• Single-cell RNA sequencing (scRNA-seq) was applied to a CLL case at diagnosis and relapse after Fludarabine, Cyclophosphamide, Rituximab (FCR) treatment.
• A significant decrease in CD19 expression was observed during disease progression.
• Computational analysis identified a major clonal switch during treatment, with a dominant clone emerging at relapse.

Findings:

• The relapsed clone exhibited 17p and 3p chromosomal deletions and upregulated pathways in motility, cytokine signaling, and antigen presentation.
• scRNA-seq revealed this aggressive clone was present at low frequency at diagnosis.
• The dominant clone displayed features of plasma cell differentiation, indicating a more aggressive phenotype.

Implications:

• Single-cell profiling of CLL heterogeneity at diagnosis is beneficial for identifying potentially aggressive clones.
• This approach can aid in recognizing underrepresented clones and informing optimal treatment strategies for CLL patients.