| Hypercholesterolemia is a known risk factor for many cancers, including Chronic Lymphocytic Leukemia (CLL). CLL is incurable with conventional chemotherapy and it would be valuable to develop strategies to prevent CLL cells from progressing to the point of causing symptoms that require treatment. Statin drugs have been shown to prolong the time to first chemotherapy treatment, suggesting that one strategy to slow the progression of CLL may be to lower levels of low-density lipoprotein (LDL)-cholesterol. The studies in this thesis were designed to investigate how LDLs affect CLL cells. The results indicate that LDLs enhance a number of signaling pathways in CLL cells in vitro that are associated with leukemic growth. These biological effects depend on the internalization and subsequent breakdown of LDL particles into various components. Overall, the results provide a biological rationale for using methods to decrease LDL-cholesterol such as diet and/or statins to slow disease progression. |
