Expression of the lung resistance protein predicts poor outcome in patients with multiple myeloma

Expression of the lung resistance protein (LRP) is associated with resistan ce to various anticancer drugs including melphalan and, therefore, may affe ct the clinical outcome in multiple myeloma (MM), To determine the clinical significance of LRP, we have compared LRP expression in bone marrow plasma cells,vith clinical parameters including response to chemotherapy and surv ival of previously untreated patients with MM (n = 72), LRP expression immu nocytochemically assessed by means of the LRP-56 monoclonal antibody was po sitive (greater than or equal to 10% staining plasma cells) in 44 (61%) sam ples. There was no correlation between LRP expression and age, sex, type of the paraprotein, serum creatinine, stage, beta(2)-microglobulin, serum lac tate dehydrogenase, or C-reactive protein. However, LRP expression was more frequently observed in patients with a p53 deletion than in those without such a deletion (P = 0.01), The overall response rate for all of the patien ts evaluable for response to induction chemotherapy (n = 58) was 67%, The r esponse rate was 87% for patients without LRP expression but only 54% for p atients with LRP expression (P = 0.01), Kaplan-Meier analysis revealed that patients with LRP expression had a shorter overall survival (median, 33 mo nths) than those without LRP expression (median not reached; P = 0.04), The se data show that LRP expression is an important marker for clinical drug r esistance and predicts a poor outcome in MM.