Microenvironmental-Mediated Regulation of L-Selectin in Chronic Lymphocytic Leukaemia

• Published in: Blood 2015-12, Vol.126 (23), p.4133-4133
• Main Authors: Brophy, Sarah, Browne, Paul, Vandenberghe, Elisabeth A., O'Brien, David, McElligott, Anthony M.
• Format: Article
• Language: English
• ISSN: 0006-4971; 1528-0020
• DOI: 10.1182/blood.V126.23.4133.4133

Chronic Lymphocytic Leukaemia (CLL) is characterized by the accumulation of CD5/19+ve B cells in the blood, bone marrow and lymph nodes. The tumour microenvironment of the bone marrow and secondary lymphoid organs promotes cell proliferation, survival and protection from drug induced apoptosis. Selectins, integrins and chemokines mediate the trafficking of CLL cells to these protective niches. An important adhesion molecule in this process is L-selectin (CD62L) which is involved in initial tethering and rolling of CLL cells in the high endothelial venules, allowing migration between the blood and the secondary lymphoid organs. It has been shown that CLL cell expression of CD62L increases during in vitro culture and blocking antibodies cause an increase in apoptosis, suggesting a role for CD62L in cell survival (Burgess et al., Clin Cancer Res. 2013). The B-cell receptor (BCR) signalling pathway is the most important pathway involved in micro-environmental crosstalk and CLL cell survival, and has recently been shown to interact with the STAT3 signalling pathway (Rozovski et al., Blood 2014). In this study, Hs5 Bone Marrow Stromal Cell (BMSC), Human Umbilical Vein Endothelial cells (HUVEC) and patient derived BMSC co-cultures were used to mimic pro-survival microenvironmental signals and investigate the effect on the expression of a panel of cell surface adhesion molecules. These coculture models resulted in a significant increase in CD62L positive CLL cells (p