Abstract
Introduction: Multiple Myeloma (MM) is an incurable hematological malignancy affecting plasma cells marked by highly heterogeneous survival rate. Relapse is a significant impediment to the successful treatment of MM clinically. One of the main causes for relapse is drug resistance to cancer chemotherapy. Currently risk stratification to MM sub -groups and categorization of complete response to therapy are assessed based on molecular, cytogenetic markers using bone marrow biopsy as available systemic markers are incompetent in this regard. We are exploring the clinical significance of our recent in vitro and in vivo findings of a novel non-genetic basis to MDR whereby tiny vesicles called microparticles (MPs) shed from cancer cell's surface transfer MDR phenotype intercellularly. MP isolated from the blood of patients who suffer from Multiple Myeloma will be phenotyped for resistance, adhesion and dissemination markers and assessed whether these characteristics are predictive of treatment outcome.
Materials and Methods: We have analysed 44 de-identified Multiple Myeloma patients. The platelet free plasma was ultracentrifuged, MM- derived microparticles were identified and quantified with flow cytometry using Annexin V450, CD138 APC, P-glycoprotein -FITC in BD TruCount tubes. Also platelet derived MPs were identified and excluded using CD41a PE and compared to age-matched healthy volunteers. Western blot analysis was conducted on microparticle lysate probing for the presence of Lung-resistance related protein (LRP).
Results: Plasma cell derived MPs were identified based on the CD138 expression from the peripheral blood plasma of MM patients. The number of systemic microparticles was found to be significantly higher in MM patients compared to the healthy volunteers. Also the systemic microparticles carried the drug resistance markers.
Conclusions: There are elevated numbers of microparticles in MM that potentially correlate with tumour aggressiveness and they carried MDR phenotypes systemically. Phenotyping MM –derived microparticles holds the potential for a non-invasive personalised systemic biomarker to predict therapeutic response.
Citation Format: Rajeev S. Krishnan, Frederick Luk, R. D. Brown, Y. L. Kwan, Mary Bebawy. A novel personalized therapeutic management in multiple myeloma. [abstract]. In: Proceedings of the AACR Precision Medicine Series: Drug Sensitivity and Resistance: Improving Cancer Therapy; Jun 18-21, 2014; Orlando, FL. Philadelphia (PA): AACR; Clin Cancer Res 2015;21(4 Suppl): Abstract nr B52.
RSS Feeds