Correlation of rhodamine 123 efflux by neoplastic plasma cells with clinical and biological characteristics of multiple myeloma

Although a variable proportion of multiple myeloma patients can achieve res ponse with conventional chemotherapy, residual tumor cells, which are refra ctory, finally reemerge leading to disease progression. The expression of t he multidrug resistance protein (MDR1) has been one of the most extensively explored mechanisms of drug resistance and has been related to a poor resp onse to chemotherapy in several human tumors, Nevertheless, a careful analy sis of the literature on MDR1 expression in multiple myeloma (MM) shows the existence of disturbing discrepancies as regards both the incidence of MDR 1 over-expression and its clinical value. A prerequisite for the assessment of MDR1 in tumor cells should be the identification of the neoplastic cell s present in the sample, This is particularly important in MM, where the pe rcentage of tumor cells in bone marrow (BM) is relatively low, In the prese nt study we have analyzed the functional expression of MDR1 in BM plasma ce lls (PC), from a group of 40 untreated MM patients. For that purpose, the r hodamine 123 efflux assay was used in combination with specific staining fo r plasma cells (CD38 strong+). The mean fluorescence channel (MFC) of rhoda mine 123 in myelomatous PC from MM patients was 311 and 110 after incubatin g cells with this fluorochrome for 15 and 60 min, respectively, The median percentage of rhodamine 123 elimination by BM PC was of 61% (range: 0.29 to 88%), Upon analyzing the relationship between the ability of myelomatous P C to eliminate rhodamine 123 and other clinical and biological disease char acteristics we found that, within the group of patients displaying high MDR 1 expression (>61% rhodamine efflux), there was a higher incidence of cases with bone disease (P = 0.014) and advanced clinical stages (P = 0.031), gr eater calcium (P = 0.007) and creatinine serum levels (P = 0.061), and lowe r levels of albumin in serum (P = 0.015), All these parameters are usually associated with a poor prognosis, When we analyzed the possible relationshi p between the ability of BM PC to eliminate rhodamine 123 and the presence of numerical chromosome abnormalities we observed that a low MDR1 expressio n was related to a higher incidence of trisomies of chromosomes 6 and 17, a lthough these differences did not reach statistical significance (P = 0.06) , In spite of these associations, from the prognostic point of view, MDR1 e xpression did not correlate with other relevant prognostic factors, respons e to treatment (P = 0.38) or overall survival (P = 0.12), Cytometry (Comm, Clin. Cytometry) 38: 24-29, 1999. (C) 1999 Wiley-Liss, Inc.