DESCRIPTION: B-Chronic Lymphocytic Leukemia (B-CLL) is a clonal B cell disorder that represents the most common leukemia in North America. We have also recently determined that abnormal angiogenesis (blood vessel formation) exists in the marrows of patients with B-CLL. Importantly, we have also determined that circulating clonal B cells and T cells contain specific cytokines/vascular growth factors that may mediate this abnormal angiogenesis. Our hypothesis is that these immune cells produce and secrete factors that are critical in the induction and maintenance of abnormal angiogenesis and B-CLL. Since angiogenesis has now been shown to be necessary for solid tumor growth and metastatic potential, the same may be true for this common human B cell malignancy. Therefore, we intend to study B-CLL patients entering onto an NCCTG clinical trial using oral thalidomide, an agent with potential anti-angiogenic activity to determine if these patients respond to this therapy and if this response is associated with changes in the angiogenic activity seen in B-CLL. In specific, we will evaluate the association of blood, urine and clonal B cell synthesized proteins that have either pro angiogenic or anti-angiogenic growth factor potential with the abnormal angiogenic marrow patterns in B-CLL. We will also determine if the CLL B cell secreted products can directly stimulate human vascular tissue. We believe that that this approach will allow us to determine the relationship/association of biologic parameters in B-CLL that mediate the abnormal blood vessel patterns known to be present in B-CLL patients. We may identify CLL patients who respond to thalidomide with repair of the abnormal angiogenic patterns and reduction in the cellular production and secretion of angiogenic growth factors. This latter finding would strongly suggest that maneuvers to alter the angiogenic potential in B-CLL patients would be an important and novel therapeutic approach in this disease.
|Effective start/end date||3/1/01 → 2/28/04|
- National Institutes of Health: $141,100.00
- National Institutes of Health: $140,237.00