Objective: To investigate the expression profile of potential therapeutic biomarkers in plasma cell myeloma (PCM) by multicolor flow cytometry analysis.Methods: Bone marrow (BM) specimens were collected consecutively and analyzed using a routine PCM panel (CD38/CD138/CD45/CD19/CD20/CD28/CD56/CD117, cyto-kappa/lambda). The specimens were further assessed for CD30, CD44, CD49d, CD70, CD105, and CD184 expression in cases containing a substantial number of neoplastic plasma cells.Results: Totally, 101 patient BM samples were assessed, including 58 men and 43 women, with a median age of 64 years (34-89). Twenty-nine patients had newly diagnosed/untreated PCM, 40 had persistent/residual disease undergoing various therapies and 32 had relapsed disease. CD49d was expressed brightly and uniformly in all 45 patients tested. Expression of CD44 and CD184 was more variable with a median percentage of 77% (1-100) and 65% (5-100) respectively. Using an arbitrary 20% cutoff, CD44 was positive in 74 (73%) and CD184 in 92 (91%) cases with a mean fluorescence intensity ratio of 42.8 and 21.4. A higher CD44 expression was observed in patients with recurrent/persistent disease (P 5 0.028). Additionally, both CD44 (P 5 0.002) and CD184 (P 5 0.026) showed higher expressions in CD117-positive cases, but there was no correlation with cytogenetic groups. The CD30, CD70, and CD105 were expressed very infrequently in PCM, with a median expression of 0.2%, 0.2%, and 0.4% respectively.Conclusions: CD49d, CD44, and CD184, are highly expressed in PCM. CD49d expression is bright and uniform, whereas CD44 and CD184 are more heterogeneous. In contrast, surface CD30, CD70, and CD105 are infrequent. These data provide useful preclinical information for the design of potential novel targeted therapies in PCM patients. Despite of recent advances (1,2), plasma cell myeloma (PCM) remains an incurable disease and new approaches that induce long-term tumor regression and improve disease outcome are needed. Immunotherapy that targets tumor-associated antigens (TAAs) has been shown to be an effective treatment approach in cancer therapy, particularly for diseases re-emerging after therapy, and a number of new agents have been developed. Brentuximab vedotin, a monoclonal antibody (mAb)-monomethyauristatin E conjugate that targets CD30, was recently approved by the Federal Drug Administration for use in patients with re-