HIGH EXPRESSION OF THE MULTIDRUG-RESISTANCE P-GLYCOPROTEIN IN HIGH-RISK MYELODYSPLASIA IS ASSOCIATED WITH IMMATURE PHENOTYPE

The expression of the multidrug resistance (MDR-1) gene product, P-170 glycoprotein (P-170) was investigated in 26 patients with low-risk (n = 9) or high-risk (n = 17) myelodysplastic syndrome (MDS), using a pa nel of monoclonal antibodies to P-170 (C219, JSB1, C494, MRK16) and qu antitative analysis of MDR-1 mRNA. P-170 membrane staining was demonst rated in bone marrow blast cells of 14/17 HR-MDS and in 2/9 LR-MDS pat ients (p < 0.01). P-170 expression was associated with the presence of blast cells characterized by an immature or early myeloid phenotype a s defined by CD34 expression (p = 0.034), CD13 or CD33 expression (p = 0.0006), or CD13/33 plus terminal deoxynucleotidyl transferase (TdT) double expression (p = 0.04). With double fluorescence analysis, P-170 expression was observed in a subset of CD34+ cells, but not in CD34- cells. P-170 expression was present in 13/15 (86%) patient samples wit h an abnormal karyotype as compared with 3110 samples (30%) with a nor mal karyotype (p < 0.05). Nine of these 15 patients had a loss or a de letion of chromosome 7. Thirteen out of 16 (81%) MDR-1 positive patien ts developed acute leukemia versus two of ten (20%) MDR-1 negative pat ients (p = 0.025). It is concluded that MDR-1 expression in MDS is pre sent in cells with an immature phenotype and is frequently observed in patients who have an abnormal karyotype and a high risk of leukemic t ransformation.