Survival mechanisms in B lymphoid malignancies and associated therapies
Abstract
The apoptotic pathway plays critical roles in regulating lymphocyte survival
throughout B cell development, maturation and differentiation. The whole
process involves clonal expansion. In the normal B lymphocyte population the
majority of cells and their progenitors derived from each stage die from
induction of apoptosis under specific mechanisms of control. Failure to do so
can result in malignant transformation. This project focuses on apoptotic
pathways and associated survival mechanisms in neoplasms of lymphoid
provenance with an emphasis on B cell malignancies. The role of galectin-3,
a molecule implicated in signal transduction and apoptotic pathways, has
been investigated in both primary CLL cells and cell lines of human B lineage,
using GCS-100, a novel galectin-3 antagonist. The potential interaction
between galectin-3 and Bcl-2 and its contribution to cell death have been
explored in depth. The role of NADPH oxidase and ROS in mitochondria has
also been examined in the context of apoptosis. PK11195, a small proapoptotic
molecule, has been studied in relation to mitochondria-mediated
apoptosis. The above investigations could contribute to a rationale for
potential novel strategies in the treatment of B cell malignancies.
Authors
Su, BoCollections
- Theses [3822]