P170 glycoprotein expression and impaired anthracycline retention in chronic myeloid leukaemia.
Chronic myeloid leukaemia (CML) is a well known model of a disease refractory 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 reactivity 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 blastic phase CML cases (P = 0.01). The same cells were assayed for their ability to retain Daunorubicin and Idarubicin after 2-hours in vitro incubation with 1000 ng/ml of either drug. It was found that anthracycline cell concentration was negatively related with the degree of the reactivity to MRK-16. In accelerated and blastic phase, CML cells simultaneously expressed P170 and the stem cell related marker, CD34. These data 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 failure in Ph+ CML.
Damiani
D
D
Department of Morphologic and Clinical Research, Udine University School of Medicine, Italy.
Michieli
M
M
Michelutti
A
A
Fanin
R
R
Russo
D
D
Baccarani
M
M
D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1 / Q000502:physiology*; D000911:Antibodies, Monoclonal; D003630:Daunorubicin / Q000493:pharmacokinetics*; D018432:Drug Resistance, Multiple / Q000502:physiology; D005434:Flow Cytometry; D006801:Humans; D015255:Idarubicin / Q000493:pharmacokinetics*; D015464:Leukemia, Myelogenous, Chronic, BCR-ABL Positive / Q000188:drug therapy / Q000378:metabolism*; D015465:Leukemia, Myeloid, Accelerated Phase / Q000188:drug therapy / Q000378:metabolism*; D015466:Leukemia, Myeloid, Chronic-Phase / Q000188:drug therapy / Q000378:metabolism*
D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1; D000911:Antibodies, Monoclonal; D015255:Idarubicin; D003630:Daunorubicin