Work

Functional Intraclonal Heterogeneity in Chronic Lymphocytic Leukemia: Proliferation vs. Quiescence

Year: 2025

Type: article

Abstract: Chronic lymphocytic leukemia (CLL) is an indolent malignancy with modest proliferation in the lymph nodes and accumulation of quiescent B cells in the peripheral blood. Targeted agents, including BTK inhibitors such as ibrutinib and the BCL2 antagonist venetoclax, have transformed therapy by disrupting proliferation, survival, and lymph node retention of CLL cells, yet CLL remains incurable. Recent studies reveal that CLL cells exist along a spectrum of proliferating, activated, and quiescent states, with dynamic transitions that shape intraclonal behavior. Whilst proliferation occurs mainly in lymph nodes, most emigrant cells in the peripheral blood become quiescent, with only a minority remaining activated. Quiescent, activated, and proliferating fractions display distinct phenotypes and CXCR4 and CD5 levels can be used to distinguish these states in the CLL life cycle. While proliferating and activated cells are more susceptible to BTK inhibition, quiescent subsets show greater sensitivity to BCL2 blockade. These functional differences, together with emerging evidence that phenotypic markers may correlate with residual disease activity, point to potential translational significance. Understanding how CLL cells switch between proliferative, activated and quiescent states will be important to uncover novel vulnerabilities and inform rational treatment strategies.

Source: Lymphatics

DOI: 10.3390/lymphatics3040047

Authors: Daniel Friedman, Piers E. M. Patten, Robbert Hoogeboom

Institutions: King's College London, King's College Hospital

Language: English

Topic: Chronic Lymphocytic Leukemia Research

Subfield: Genetics

Field: Medicine

Domain: Health Sciences

SDG: Good health and well-being

Open Access status: gold

Estimated APC paid: $1,207