Work

Proliferating CLL cells express high levels of CXCR4 and CD5

Year: 2024

Type: article

Abstract: Chronic Lymphocytic Leukaemia (CLL) is an incurable progressive malignancy of CD5+ B cells with a birth rate between 0.1-1% of the entire clone per day. However, the phenotype and functional characteristics of proliferating CLL cells remain incompletely understood. Here, we stained peripheral blood CLL cells for ki67 and DNA content and found that CLL cells in G1-phase have a CXCR4 lo CD5 hi phenotype, whilst CLL cells in S/G2/M-phase express high levels of both CXCR4 and CD5. Induction of proliferation in vitro using CD40L stimulation results in high ki67 levels in CXCR4 lo CD5 hi cells with CXCR4 expression increasing as CLL cells progress through S and G2/M-phases, whilst CXCR4 hi CD5 lo CLL cells remained quiescent. Dye dilution experiments revealed an accumulation of Ki67 hi divided cells in the CXCR4 hi CD5 hi fraction. In Eμ-TCL1 transgenic mice, the CXCR4 hi CD5 hi fraction expressed high levels of ki67 and was expanded in enlarged spleens of diseased animals. Human peripheral blood CXCR4 hi CD5 hi CLL cells express high levels of IgM and the chemokine receptors CCR7 and CXCR5 and migrated most efficiently towards CCL21. We found higher levels of CXCR4 in patients with progressive disease and the CXCR4 hi CD5 hi fraction was expanded upon clinical relapse. Thus, this study defines the phenotype and functional characteristics of proliferating CLL cells identifying a novel subclonal population that underlies CLL pathogenesis and may drive clinical outcome.

Source: HemaSphere

DOI: 10.1002/hem3.70064

Authors: Daniel Friedman, Drshika P. Mehtani, Jennifer B. Vidler, 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: $2,250