title: Bone marrow stromal mesenchymal cells induce down regulation of CD20 expression on B-CLL: implications for rituximab resistance in CLL.
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.
authors.affiliation: Unidad de Terapia Celular, Laboratorio de Patología Celular y Molecular, Centro de Medicina Experimental, Instituto Venezolano de Investigaciones Científicas (IVIC), Caracas, Venezuela.
authors.forename: Maria-Elena
authors.initials: ME
authors.lastname: Marquez
authors.forename: Octavio
authors.initials: O
authors.lastname: Hernández-Uzcátegui
authors.forename: Alejandro
authors.initials: A
authors.lastname: Cornejo
authors.forename: Paula
authors.initials: P
authors.lastname: Vargas
authors.forename: Osiris
authors.initials: O
authors.lastname: Da Costa
mesh_terms: D058846:Antibodies, Monoclonal, Murine-Derived / Q000494:pharmacology / Q000627:therapeutic use; D000920:Antibody-Dependent Cell Cytotoxicity / Q000276:immunology; D018951:Antigens, CD20 / Q000235:genetics / Q000378:metabolism*; D000970:Antineoplastic Agents / Q000494:pharmacology / Q000627:therapeutic use; D017209:Apoptosis; D018957:CD59 Antigens / Q000235:genetics / Q000378:metabolism; D002450:Cell Communication; D018920:Coculture Techniques; D015536:Down-Regulation; D019008:Drug Resistance, Neoplasm / Q000235:genetics; D015870:Gene Expression; D006801:Humans; D015451:Leukemia, Lymphocytic, Chronic, B-Cell / Q000188:drug therapy / Q000235:genetics / Q000378:metabolism*; D059630:Mesenchymal Stem Cells / Q000187:drug effects / Q000378:metabolism*; D000069283:Rituximab
chemical_list: D058846:Antibodies, Monoclonal, Murine-Derived; D018951:Antigens, CD20; D000970:Antineoplastic Agents; D018957:CD59 Antigens; D000069283:Rituximab
keywords: CD20; chronic lymphocytic leukaemia; mesenchymal stromal cells; rituximab