Abstract
Progressive cases of B-cell chronic lymphocytic leukemia (CLL) are frequently associated with lymphadenopathy, highlighting a critical role for signals emanating from the tumor environment in the accumulation of malignant B cells. We investigated on CLL cells from 30 untreated patients the consequence of B-cell receptor (BCR) triggering on the membrane expression of CXCR4 and CD62L, two surface molecules involved in trafficking and exit of B-lymphocytes from lymph nodes. BCR stimulation promoted a strictly simultaneous down-regulation of CXCR4 and CD62L membrane expression to a variable extent. The variable BCR-dependent decrease of the two proteins was strikingly representative of the heterogeneous capacity of the CLL cells to respond to BCR engagement in a given patient. Functionally, cells down-regulating CXCR4 and CD62L in response to BCR engagement displayed a reduction in both migration toward CXCL12 and adhesion to lymphatic endothelial cells. Remarkably, the ability of CLL cells to respond to BCR ligation was correlated with unfavorable prognostic markers and short progression-free survival. In conclusion, BCR signaling promotes decrease of CXCR4 and CD62L membrane expression in progressive cases only. These results are consistent with the hypothesis that BCR-mediated signaling pathways favor accumulation of a proliferative pool within the lymph nodes of progressive CLL cases.
Highlights
Chronic lymphocytic leukemia (CLL) is characterized by a highly variable clinical course
We previously showed that B-cell receptor (BCR) engagement promoted in vitro CLL cell survival in patients with progressive disease and unfavorable prognostic markers only [22]
In primary CLL cells, we show that in vitro BCR engagement led to the decrease of CXCR4 and CD62L membrane expression, in particular in cells from patients with unfavorable prognostic factors and at risk of disease progression
Summary
Chronic lymphocytic leukemia (CLL) is characterized by a highly variable clinical course. Aggressive CLLs are associated with enlarged lymph nodes (LN) and splenomegaly resulting from the accumulation of malignant B lymphocytes within secondary lymphoid organs [1, 2]. This indicates that the recirculation process of CLL cells from blood to lymphoid tissues might be crucial for CLL cells accumulation and survival and highlights the predominant role of the tumor microenvironment in the pathogenesis of CLL [3, 4]. Recent evidence indicates that CXCR4-CXCL12 interactions play an important role in directing the movements of lymphoid cells within secondary lymphoid organs [13]. CD62L and its lymphatic receptor may participate in the mechanisms mediating lymphocytes exit from LNs
Sign-in/Register to view highlights & summary Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
