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Updated: Apr 21, 2026
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VDJ-Seq: Deep Sequencing Analysis of Rearranged Immunoglobulin Heavy Chain Gene to Reveal Clonal Evolution Patterns of B Cell Lymphoma
Published on: December 28, 2015
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Therapy-driven clonal dynamics in chronic lymphocytic leukemia
Larry Mansouri1, Thomas Chatzikonstantinou2, Lydia Scarfò3
1Department of Molecular Medicine and Surgery, Karolinska Institutet, Stockholm, Sweden.
Seminars in Cancer Biology
|April 19, 2026
Summary
Chronic lymphocytic leukemia (CLL) evolves with diverse genetic changes, leading to treatment resistance. Understanding clonal evolution is key to developing personalized therapies for better patient outcomes.
Area of Science:
- Hematology
- Genomics
- Cancer Biology
Background:
- Chronic lymphocytic leukemia (CLL) is characterized by intraclonal diversity and complex clonal architecture.
- Genetic alterations in signaling pathways, DNA damage response, and apoptosis drive CLL progression and therapeutic resistance.
Purpose of the Study:
- To review current knowledge on clonal evolution and resistance mechanisms in CLL.
- To discuss emerging technologies and future research directions for personalized CLL treatment.
Main Methods:
- Genomic profiling to identify genetic alterations.
- Analysis of resistance mechanisms to chemoimmunotherapy and targeted agents.
- Review of single-cell sequencing and multi-omics approaches.
Main Results:
- Chemoimmunotherapy resistance is linked to TP53 aberrations and resistant microclones.
- Targeted therapies select for specific mutations (e.g., BTK, PLCG2) and alternative survival pathways.
- Clonal evolution significantly impacts disease progression and treatment response.
Conclusions:
- Understanding CLL clonal evolution is crucial for developing personalized therapeutic strategies.
- Future research should address resistance in evolving treatment contexts like combination therapies and cellular therapies.
- Improved insights into clonal dynamics will enhance long-term outcomes for CLL patients.
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