Significantly lower P-glycoprotein expression in acute promyelocytic leukemia than in other types of acute myeloid leukemia: immunological, molecular and functional analyses.
Expression of P-glycoprotein (Pgp), the product of the multidrug resistance (MDR1) gene, detected by flow cytometric analysis of the binding of antibody 4E3.16, was found on significantly fewer leukemic cells in 35 adult patients with de novo acute promyelocytic leukemia (APL) (mean 14.8%, median 7%) than in 184 patients with non-APL acute myeloid leukemia (AML) at diagnosis (mean 28.3%, median 18%) (p = 0.0038). APL was diagnosed based on morphology, the detection of t(15;17) and of the chimeric fusion transcript PML/RAR alpha by PCR. To further substantiate low MDR1 expression in APL, we studied cells from 11 APL patients at the molecular and functional level in comparison to 48 non-APL cases. The diagnosis of APL was associated with the absence of Pgp function by the rhodamine efflux assay (p = 0.0001). Furthermore, MDR1-specific transcript levels, determined by quantitative PCR with two distinct sets of primers, were significantly lower in mononuclear cells from the APL than the other AML cases (p = 0.013). The frequency of leukemic cells positive for CD34, an antigen presumably associated with Pgp expression in AML, was significantly lower in APL than other AMLs (p = 0.0001). In contrast to non-APL leukemias, those few cases of CD34 strongly positive APL neither expressed Pgp nor contained significant MDR1 transcript levels. Low expression of Pgp by APL cells may provide the biologic basis for the high sensitivity of this leukemia subtype to chemotherapeutic agents in vivo.
Paietta
E
E
Department of Oncology, Montefiore and Albert Einstein Cancer Center, Bronx, New York.
Andersen
J
J
Racevskis
J
J
Gallagher
R
R
Bennett
J
J
Yunis
J
J
Cassileth
P
P
Wiernik
P H
PH
D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1; D000208:Acute Disease; D000911:Antibodies, Monoclonal; D000912:Antibodies, Neoplasm / Q000032:analysis; D015703:Antigens, CD; D001483:Base Sequence; D002352:Carrier Proteins / Q000032:analysis / Q000235:genetics / Q000502:physiology*; D004351:Drug Resistance; D006801:Humans; D007951:Leukemia, Myeloid / Q000235:genetics* / Q000378:metabolism / Q000503:physiopathology*; D015473:Leukemia, Promyelocytic, Acute / Q000235:genetics / Q000378:metabolism / Q000503:physiopathology*; D051917:Leukosialin; D008562:Membrane Glycoproteins / Q000032:analysis / Q000235:genetics / Q000502:physiology*; D008969:Molecular Sequence Data; D016133:Polymerase Chain Reaction; D012313:RNA / Q000235:genetics / Q000378:metabolism; D012680:Sensitivity and Specificity; D012795:Sialoglycoproteins / Q000502:physiology; D013194:Staining and Labeling; D014158:Transcription, Genetic
D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1; D000911:Antibodies, Monoclonal; D000912:Antibodies, Neoplasm; D015703:Antigens, CD; D002352:Carrier Proteins; D051917:Leukosialin; D008562:Membrane Glycoproteins; C465014:SPN protein, human; D012795:Sialoglycoproteins; D012313:RNA