P170 GLYCOPROTEIN EXPRESSION AND IMPAIRED ANTHRACYCLINE RETENTION IN CHRONIC MYELOID-LEUKEMIA

Chronic myeloid leukaemia (CML) is a well known model of a disease ref ractory to chemotherapy, including anthracyclines and other drugs that are believed to be pumped out of the cells by a 170 Kd transmembrane glycoprotein (P170). In 35 cases of Ph+ CML we investigated the reacti vity of leukaemic cells to a P170-directed monoclonal antibody (MRK-16 ), by means of flow cytometry. P170 overexpression was found in 4/14 ( 29%) chronic phase CML cases and in 16/23 (70%) accelerated and blasti c phase CML cases (P = 0.01). The same cells were assayed for their ab ility to retain Daunorubicin and Idarubicin after 2-hours in vitro inc ubation with 1000 ng/ml of either drug. It was found that anthracyclin e cell concentration was negatively related with the degree of the rea ctivity to MRK-16. In accelerated and blastic phase, CML cells simulta neously expressed P170 and the stem cell related marker, CD34. These d ata confirm that Ph+ leukaemic cells overexpress P170, show that P170 overexpression is functionally relevant, and suggest that P170-related multidrug resistance may be an important factor for chemotherapy fail ure in Ph+ CML.