Increased expression of the multidrug resistance-associated protein gene in relapsed acute leukemia.
Quantitative reverse transcriptase polymerase chain reaction (RT-PCR) was used to determine relative levels of transcripts for MDR1 and the recently described multidrug resistance-associated protein (MRP) in normal lymphohematopoietic cells and in 62 bone marrow aspirates of newly diagnosed and recurrent acute leukemia. Levels of MRP expression in newly diagnosed AML samples were similar to those observed in normal bone marrow cells (CD34-negative and CD34-positive) and in unselected HL60 human promyelocytic leukemia cells, which were used as an internal control throughout this study. In contrast, samples of AML obtained at the time of relapse contained approximately twofold higher levels of MRP RNA (P < .01). Analysis of paired samples, the first obtained at diagnosis and the second at relapse, from 13 acute myelogenous leukemia (AML) and four acute lymphocytic leukemia (ALL) patients showed that MRP expression was increased at the time of relapse in greater than 80% of patients. In contrast, no consistent changes of MDR1 expression at relapse were observed. These results raise the possibility that increased MRP expression might contribute to leukemic relapse.
Schneider
E
E
Medicine Branch, National Cancer Institute, Bethesda, MD 20892.
Cowan
K H
KH
Bader
H
H
Toomey
S
S
Schwartz
G N
GN
Karp
J E
JE
Burke
P J
PJ
Kaufmann
S H
SH
D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1 / Q000235:genetics; D018528:ATP-Binding Cassette Transporters / Q000235:genetics*; D015703:Antigens, CD / Q000032:analysis; D018952:Antigens, CD34; D018432:Drug Resistance, Multiple / Q000235:genetics*; D015870:Gene Expression; D006801:Humans; D015470:Leukemia, Myeloid, Acute / Q000235:genetics* / Q000276:immunology; D015473:Leukemia, Promyelocytic, Acute / Q000235:genetics; D027425:ATP-Binding Cassette, Sub-Family C Proteins; D016133:Polymerase Chain Reaction; D054198:Precursor Cell Lymphoblastic Leukemia-Lymphoma / Q000235:genetics; D012333:RNA, Messenger / Q000378:metabolism; D012194:RNA-Directed DNA Polymerase; D012008:Recurrence; D014407:Tumor Cells, Cultured
D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1; D018528:ATP-Binding Cassette Transporters; D015703:Antigens, CD; D018952:Antigens, CD34; D027425:ATP-Binding Cassette, Sub-Family C Proteins; D012333:RNA, Messenger; D012194:RNA-Directed DNA Polymerase