Developing a 3D chronic lymphocytic leukemia (CLL) microenvironment
No Thumbnail Available
Date
2020-10-02
Authors
Choquette, Tricia
Journal Title
Journal ISSN
Volume Title
Publisher
Abstract
Chronic Lymphocytic Leukemia (CLL) is characterized by the accumulation of monoclonal B lymphocytes in the blood, lymph nodes, bone marrow and spleen. These microenvironments provide a protective niche for CLL cells that promote CLL cell survival and drug resistance. The dependence of CLL cells on their microenvironments in vivo is depicted by the spontaneous apoptosis CLL cells undergo when cultured alone in vitro. Co-culture of CLL cells with accessory cells or other components of the microenvironment such as cytokines, has been shown to counteract this spontaneous apoptosis of CLL cells, and has also been shown to be effective at preventing apoptosis from a variety of treatments. The dependence of CLL cells on their 3D microenvironment illustrates the need to develop a three-dimensional (3D) cell culture system for CLL, that incorporates components of their microenvironment in vivo, in order to develop research tools to explore new therapeutic targets. There are limited methods to study the CLL microenvironment, such as adaptations of two-dimensional (2D) cell culture and animal models. The objective of this thesis is to develop a 3D cell culture model for CLL that incorporates the microenvironment. Drug resistance remains a significant clinical barrier to treat CLL patients, where treatments are initially effective, but the disease often relapses. By understanding the role microenvironment factors play in promoting CLL cell survival during treatment, effective therapeutic strategies could be developed to overcome drug resistance.
Description
Keywords
CLL, Microenvironment, ACCER
Citation
Chicago