Sample Quarterly Report  

Quarterly Progress Report: February 1, 2001- April 30, 2001 S. Vincent Rajkumar, MD Angiogenesis in Plasma Cell Disorders

Overall work on the grant is proceeding extremely well. Our research efforts were highlighted when I was invited to chair the Angiogenesis session at the recently concluded VIIIth International Myeloma Workshop held at Banff. For the first year of the grant, we continue to focus on specific Aims 1 and 3.

Equipment: We have received approval from Mayo Foundation for the purchase of a sophisticated real time RT-PCR system (Cost $65,000 paid by Mayo Research Budget). The system has been ordered and delivery is expected in the next 1-2 weeks. This quantitative RT-PCR system would greatly improve our ability to assess changes in levels of expression of VEGF and its receptors accurately. The approval of the purchase of this equipment also indicates Mayo's commitment to this research.

Technician: Jessica Haug, the technician on this grant continues to do an outstanding job. She attended the VIIIth International workshop in Banff, and continues to initiate collaborations with other investigators in the field.

Research Activity: For specific aim 1 of the primary objectives, staining of plasmacytoma and bone marrow samples for CD34 by immunohistochemistry to identify microvessels has been completed. We are in the process of analyzing the slides. The goal is to have an abstract for ASH 2001. Staining for VEGF and bFGF will be done subsequently. For specific aim 2, Mike Timm, a technician in the laboratory is familiar with the model. We are not planning to initiate studies until Year 2 of the grant. The studies necessary for this model need to be batched to minimize the use of animals. IACUC approval is pending. An alternative in-vitro Angiogenesis kit that would perform the same functions as the rat aortic ring assay more efficiently has been ordered and we will be evaluating this shortly. For specific aim 3, RT-PCR techniques have detected VEGF and Flt-1 expression in all of the myeloma cell lines and patient samples tested. Four of the nine cell lines also expressed the second VEGF receptor KDR. A manuscript on the expression of VEGF and its receptors by MM cells is being prepared for submission to Blood. We have set up assays and are now looking at the effect of VEGF on myeloma cell growth and apoptosis. A flow cytometric assay for VEGF in myeloma cells is also being developed. RNA is being extracted from patient samples to run quantitative RT_PCR assays on the new real time RT-PCR machine. Jessica Haug has become familiar with the real time RT-PCR system by working in the Mayo molecular labs that now possess the machine.

Publications in which the Goldman Foundation support has been acknowledged (Publications 5 and 6 are new since last report):

1. Rajkumar SV, Fonseca R, Dispenzieri A, Lacy MQ, Lust JA, Greipp PR, Witzig TE, Kyle RA, Gertz MA. Thalidomide in the treatment of relapsed and refractory myeloma. Mayo Clinic Proceedings 2000; 75:897-901 2. Rajkumar SV, Witzig TE. A review of Angiogenesis and anti-antigenic therapy with thalidomide in multiple myeloma. Cancer Treat Rev 2000; 26:351-362. 3. Rajkumar SV. Thalidomide in multiple myeloma. Oncology 2000; 14 (Suppl 13): 11-15. 4. Rajkumar SV, Fonseca R, Dispenzieri A, Lacy MQ, Witzig TE, Lust JA, Larson D, Therneau TM, Greipp PR, Kyle RA, Gertz MA. Effect of complete response on outcome following autologous stem cell transplantation for myeloma. Bone Marrow Transplantation 2000; 26:979-983. 5. Rajkumar SV, Dispenzieri A, Fonseca R, Lacy MQ, Geyer S, Lust JA, Kyle RA, Greipp PR, Gertz MA, Witzig TE. Thalidomide for previously untreated indolent or smoldering multiple myeloma. Leukemia (In Press). 6. Rajkumar SV. Thalidomide in cancer. Oncology (In Press).