Expression of the multidrug resistance-associated protein (MRP) in acute and chronic leukemias.
We determined the expression of the multidrug resistance-associated protein (MRP), a new putative transmembrane drug transporter, in peripheral blood cells from healthy volunteers as well as from 60 patients with acute or chronic leukemia, using an RNase protection assay. MRP appeared to be ubiquitously expressed at low levels in all nonmalignant hemopoietic cell types, reflecting its basal constitutive expression. In acute myelocytic leukemia (AML) (n = 16), one of nine untreated patients and two of seven patients with prior chemotherapy showed significant hyperexpression of MRP. In chronic lymphocytic leukemia (CLL) (n = 21), either treated (n = 8) or untreated (n = 13), a high percentage (15 of 21: 71% had relatively high expression levels of the MRP gene. In contrast, low MRP expression levels were detected in acute lymphocytic leukemia (n = 14), and in chronic myelocytic leukemia (n = 9). DNA analysis by Southern blotting did not reveal amplification of the MRP gene in the leukemia samples, including those with elevated MRP mRNA levels. We conclude that relatively high expression of MRP is occasionally observed in AML and at high frequency in CLL, irrespective of treatment, probably due to transcriptional activation and/or increased mRNA stability.
Burger
H
H
Department of Medical Oncology, University Hospital Rotterdam, The Netherlands.
Nooter
K
K
Zaman
G J
GJ
Sonneveld
P
P
van Wingerden
K E
KE
Oostrum
R G
RG
Stoter
G
G
D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1; D000293:Adolescent; D000328:Adult; D000368:Aged; D000818:Animals; D015139:Blotting, Southern; D002352:Carrier Proteins / Q000097:blood* / Q000235:genetics; D002648:Child; D002675:Child, Preschool; D004351:Drug Resistance; D005260:Female; D015870:Gene Expression; D006413:Hematopoietic System / Q000166:cytology; D006801:Humans; D007223:Infant; D015451:Leukemia, Lymphocytic, Chronic, B-Cell / Q000097:blood* / Q000235:genetics; D015464:Leukemia, Myelogenous, Chronic, BCR-ABL Positive / Q000097:blood* / Q000235:genetics; D015470:Leukemia, Myeloid, Acute / Q000097:blood* / Q000235:genetics*; D008297:Male; D008562:Membrane Glycoproteins / Q000097:blood* / Q000235:genetics; D051379:Mice; D008875:Middle Aged; D054198:Precursor Cell Lymphoblastic Leukemia-Lymphoma / Q000097:blood* / Q000235:genetics*; D012333:RNA, Messenger / Q000032:analysis / Q000235:genetics / Q000378:metabolism; D012260:Ribonucleases / Q000378:metabolism
D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1; D002352:Carrier Proteins; D008562:Membrane Glycoproteins; D012333:RNA, Messenger; D012260:Ribonucleases