Serum Pleiotrophin Is a New Multiple Myeloma Tumor Marker That Also Predicts Clinical Status.

Pleiotrophin (PTN), an 18 kD heparin-binding protein, has been found to be expressed in some solid tumors whereas it has not been previously evaluated in hematologic malignancies. Constitutive expression of PTN promotes tumor expansion and may increase metastatic potential. This protein binds to syndecan-1 (CD138) and stimulates angiogenesis. Its role in multiple myeloma (MM), thus far, has not been evaluated. Recently, we showed that PTN was strongly expressed in MM cell lines and malignant plasma cells from fresh bone marrow samples but not in normal control bone marrow specimens. Since PTN has been shown to be elevated in the serum of some solid tumor patients, we determined whether PTN may be elevated in the serum of MM patients, and correlated these levels with the patients’ disease status. By using a highly sensitive and specific enzyme-liked immunosorbent assay (ELISA) for PTN, we tested 270 different serum samples [MM (n=194), MGUS (n=18) and age-matched healthy control subjects (n=58)]. Serum samples from MM patients were obtained at the time of diagnosis as well as during the course of their disease. Serum PTN levels were higher in MM patients than in the control subjects (median=1.44 ng/ml vs 0.42 ng/ml, p <0.0001). In addition, among patients with MGUS and smoldering myeloma, serum PTN was also higher than in the controls (median=1.14 ng/ml vs 0.42 ng/ml, p <0.0001) but lower than among patients with active MM (p <0.0001). Patients with untreated MM showed serum PTN levels similar to those patients who received prior treatment. Among previously treated patients, the group with progressive disease at the time of evaluating their PTN level had higher serum concentrations of this protein than patients with responsive or stable disease (median=1.73 ng/ml vs 1.16 ng/ml, p <0.0001). Evaluation of patients who had a change in disease status showed that the serum PTN level increased at the time of progression when compared with their baseline level (median=1.76 ng/ml vs 1.01 ng/ml, p=0.009). Conversely, patients who responded to anti-MM therapy exhibited significant decreases of PTN as compared with their pre-treatment PTN values (median=0.95 ng/ml vs 1.90 ng/ml, p=0.007). These results suggest that serum PTN may be a new tumor marker for MM, and monitoring of this protein may be useful to follow the responsiveness to therapy and disease status of MM patients. We are now undertaking studies to evaluate PTN as a prognostic marker in a large cohort of newly diagnosed MM patients.