Bone marrow stromal mesenchymal cells induce down regulation of CD20 expression on B‐CLL: implications for rituximab resistance in CLL |
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| Authors: | Maria‐Elena Marquez Octavio Hernández‐Uzcátegui Alejandro Cornejo Paula Vargas Osiris Da Costa |
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| Affiliation: | 1. Unidad de Terapia Celular, Laboratorio de Patología Celular y Molecular, Centro de Medicina Experimental, Instituto Venezolano de Investigaciones Científicas (IVIC), Caracas, Venezuela;2. Banco Municipal de Sangre de Caracas, Caracas, Venezuela |
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| Abstract: | Although the majority of B cells express surface CD20 in chronic lymphocytic leukaemia (B‐CLL), only ～50% of patients respond to treatment with rituximab. Decreased CD20 expression on these tumour B cells could be responsible for the lack of response observed in some patients treated with rituximab. Despite the potential critical role of CD20 in the biology of B cell malignancies, the mechanisms controlling its expression are poorly understood. At the bone marrow level, mesenchymal stromal cells (MSC) may regulate and support the survival of malignant cells, such as B‐CLL cells. In this study, we investigated whether MSC may regulate the CD20 expression on B‐CLL. For this purpose, B cells from CLL patients were isolated and co‐cultured on MSC. B‐CLL cells were collected from B‐CLL/MSC co‐cultures and examined for their expression of CD20. We demonstrate decreased CD20 expression in B‐CLL cells after 2 weeks of co‐culture with MSC, under contact and non‐contact conditions, which was associated with a decreased susceptibility to rituximab. Additionally, B cells co‐cultured with MSCs show an increase in CD59 expression. Our findings strongly suggest that the interaction between B‐CLL cells and MSC may play a major role in the resistance to rituximab‐induced apoptosis of B‐CLL cells. |
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| Keywords: | chronic lymphocytic leukaemia mesenchymal stromal cells CD20 rituximab |
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