Expression of multidrug resistance gene (MDR-1) in human normal leukocytes.
BACKGROUND
The mdr-1 gene, which codes for a 170-kd transmembrane glycoprotein (P170), is frequently overexpressed in multidrug resistant (MDR) tumor cell lines and in spontaneous tumors, including leukemia and lymphoma. However, it is also constitutively expressed as a normal gene in normal tissues.


METHODS
We used human mdr-1 cDNA and three anti-P170 monoclonal antibodies (MoAbs: MRK-16, C-219 and JSB-1) to investigate the normal peripheral blood leukocyte content of mdr-1 specific mRNA and of P170 through immunocytochemistry and flow cytometry.


RESULTS
We did not find any increase in mdr-1-specific mRNA, while small amounts of P170 were easily detectable in about two thirds of the lymphocytes and monocytes and in about one third of the granulocytes. The level of P170 expression in leukocytes was similar to that found in non-MDR tumor cell lines.


CONCLUSIONS
mdr-1 is constitutively expressed in human normal leukocytes at levels that cannot significantly affect drug resistance. Accordingly, low-level mdr-1 expression in leukemic cells should not be considered a label of pleiotropic drug resistance.
Damiani
D
D
Cattedra di Ematologia, Policlinico Universitario, Udine, Italy.
Michieli
M
M
Michelutti
A
A
Geromin
A
A
Raspadori
D
D
Fanin
R
R
Savignano
C
C
Giacca
M
M
Pileri
S
S
Mallardi
F
F
D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1; D000911:Antibodies, Monoclonal / Q000276:immunology; D002352:Carrier Proteins / Q000096:biosynthesis / Q000235:genetics* / Q000276:immunology; D002478:Cells, Cultured; D005434:Flow Cytometry; D015870:Gene Expression; D006801:Humans; D007124:Immunoenzyme Techniques; D007962:Leukocytes / Q000378:metabolism*; D008562:Membrane Glycoproteins / Q000096:biosynthesis / Q000235:genetics* / Q000276:immunology; D009363:Neoplasm Proteins / Q000096:biosynthesis; D012333:RNA, Messenger / Q000032:analysis; D014407:Tumor Cells, Cultured / Q000378:metabolism
D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1; D000911:Antibodies, Monoclonal; D002352:Carrier Proteins; D008562:Membrane Glycoproteins; D009363:Neoplasm Proteins; D012333:RNA, Messenger