Malignant B cells with mature-like characteristics are a hallmark of chronic lymphocytic leukemia (CLL). Chronic B-cell receptor (BCR) signaling promotes CLL cell survival, however, new research showed that CLL cells multiply in response to T-helper (Th) cells in a CD40L-dependent way. In non-malignant B cells, researchers showed that CD40L elevated CD45 phosphatase activity, and BCR signaling provided Th stimulation.
As a result, they postulated that the Th cell elevation of CD45 activity may be a crucial regulator of CLL BCR signaling and proliferation. Results showed that both Th and CLL cell CD45 activity increased in a culture system containing activated autologous Th cells, which was associated with improved downstream antigen receptor signaling and proliferation. The surface expression of CD43, a CLL immunophenotypic marker, and Galectin-1, a CD45 ligand, both rose concurrently. A proliferative CLL cell population with increased CD45 activity was characterized by the combined expression of Galectin-1 and CD43. Using monoclonal antibodies, pharmacology, or silencing techniques to target Galectin-1 or CD43 reduced CD45 activity and CLL cell growth.
The findings pointed to a mechanism by which activated T cells control CD45 activity and BCR signaling in CLL cells, suggesting that modulating CD45 phosphatase activity may be a promising CLL treatment target.