Clonal Evolution of High-Risk Chronic Lymphocytic Leukemia: A Contemporary Perspective

Overview

Journal Front Oncol

Specialty Oncology

Date 2022 Jan 3

PMID 34976831

Citations 8

Authors

Marwan Kwok

Catherine J Wu

Affiliations

Soon will be listed here.

Abstract

Clonal evolution represents the natural process through which cancer cells continuously search for phenotypic advantages that enable them to develop and expand within microenvironmental constraints. In chronic lymphocytic leukemia (CLL), clonal evolution underpins leukemic progression and therapeutic resistance, with differences in clonal evolutionary dynamics accounting for its characteristically diverse clinical course. The past few years have witnessed profound changes in our understanding of CLL clonal evolution, facilitated by a maturing definition of high-risk CLL and an increasing sophistication of next-generation sequencing technology. In this review, we offer a modern perspective on clonal evolution of high-risk CLL, highlighting recent discoveries, paradigm shifts and unresolved questions. We appraise recent advances in our understanding of the molecular basis of CLL clonal evolution, focusing on the genetic and non-genetic sources of intratumoral heterogeneity, as well as tumor-immune dynamics. We review the technological innovations, particularly in single-cell technology, which have fostered these advances and represent essential tools for future discoveries. In addition, we discuss clonal evolution within several contexts of particular relevance to contemporary clinical practice, including the settings of therapeutic resistance to CLL targeted therapy and immunotherapy, as well as Richter transformation of CLL to high-grade lymphoma.

Citing Articles

Management strategies for patients with chronic lymphocytic leukaemia harbouring complex karyotype.

Serafin A, Ruocco V, Cellini A, Angotzi F, Bonaldi L, Trentin L Br J Haematol. 2025; 206(3):832-841.

PMID: 39761654 PMC: 11886947. DOI: 10.1111/bjh.19986.

BCL2 Protein Progressively Declines during Robust CLL Clonal Expansion: Potential Impact on Venetoclax Clinical Efficacy and Insights on Mechanism.

Lee H, Haque S, Gupta R, Kolitz J, Allen S, Rai K Lymphatics. 2024; 2(2):50-78.

PMID: 39664277 PMC: 11632909. DOI: 10.3390/lymphatics2020005.

Unexpected chronic lymphocytic leukemia B cell activation by bisphosphonates.

Mazzarello A, Gugiatti E, Cossu V, Bertola N, Bagnara D, Carta S Cancer Immunol Immunother. 2024; 73(2):27.

PMID: 38280019 PMC: 10821833. DOI: 10.1007/s00262-023-03588-z.

Simulating Interclonal Interactions in Diffuse Large B-Cell Lymphoma.

Ganesh S, Roth C, Parekkadan B Bioengineering (Basel). 2023; 10(12).

PMID: 38135951 PMC: 10740451. DOI: 10.3390/bioengineering10121360.

Characterization of the Intraclonal Complexity of Chronic Lymphocytic Leukemia B Cells: Potential Influences of B-Cell Receptor Crosstalk with Other Stimuli.

Mazzarello A, Fitch M, Cardillo M, Ng A, Bhuiya S, Sharma E Cancers (Basel). 2023; 15(19).

PMID: 37835400 PMC: 10571896. DOI: 10.3390/cancers15194706.

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