Introduction: Multiple Myeloma (MM) is an incurable hematological malignancy affecting plasma cells marked by highly heterogeneous survival rates and confinement of the disease to bone marrow (BM). Relapse is a significant impediment in the clinical setting and the development of multidrug resistance (MDR) to therapy is the main cause of relapse. Currently, risk stratification to MM sub-groups and categorization of complete response to therapy are established on molecular and cytogenetic markers using bone marrow biopsies. We are exploring the clinical significance of plasma cell derived microparticles as a novel prognostic indicator in MM. Materials and Methods: We have analysed 79 de-identified MM patients and 24 normal subjects. Platelet free plasma was centrifuged and plasma cell derived MPs were identified and quantified by flow cytometry using Annexin V450, CD138 APC, anti-P-glycoprotein (P-gp)-FITC (17F9) in BD TruCount tubes. Platelet derived MPs were excluded from the analysis using CD41a-PE. All patient samples were compared to age-matched healthy volunteers. Western blot analysis was conducted on MP lysates probing for the presence of Lung-Resistance related Protein (LRP) and P-glycoprotein (P-gp). Morphology and the size of MP fraction from MM patients were investigated using scanning electron micrographs Results: The number of systemic MPs and CD138+MPs were found to be significantly higher in MM patient samples compared to the healthy volunteers. MDR markers (LRP & P-gp) were expressed on systemic MPs from relapsing MM patients. MPs from patients were spherical in shape and had smooth surface consistent with those isolated from the MM cell line OPM2.

Conclusions: There are elevated numbers of systemic MPs in all the 79 MM subjects (across all disease stages) compared to the healthy volunteers. The expressions of CD138 on MPs in the MM patients offer a sensitive assessment of disease progression and therapeutic outcome. Systemic MPs from MM patients carry a ‘snapshot’ of the less accessible bone marrow compartment and may provide a novel systemic ‘biosignature’ of MM progression and therapeutic outcome in the clinical setting. The MDR markers on systemic MPs may support dosage regimen and therapeutic decisions in MM clinical setting.

Acknowledgements: This project has ethical approval from Sydney Local Health District Human Research Ethics Committee (CRGH)- EC00118 # HREC/11/CRGH/223 (CH62/6/2011/150).

We would like to thank all the volunteers whom have contributed to this study.

Citation Format: Sabna Rajeev Krishnan, Mary Bebawy, Ross Duncan Brown, Frederick Luk, Yiulam Kwan. Microparticles as novel prognostic markers in multiple myeloma. [abstract]. In: Proceedings of the 106th Annual Meeting of the American Association for Cancer Research; 2015 Apr 18-22; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2015;75(15 Suppl):Abstract nr 5306. doi:10.1158/1538-7445.AM2015-5306