P-glycoprotein expression and prognostic value in acute myeloid leukemia.
OBJECTIVE
Drug resistance has become a major cause of treatment failure in patients with acute leukemia. P-glycoprotein (Pgp), which is associated with the multidrug resistance (MDR) phenotype, has been reported to be an important predictor of treatment outcome. The aim of this study was to analyze the value of Pgp expression in bone marrow or peripheral blood as a predictor of the response to remission induction chemotherapy as well as the duration of remission in patients with de novo acute myeloid leukemia (AML).


METHODS
We examined the expression of Pgp in 82 patients with de novo AML using an immunocytochemical assay with the C219 monoclonal antibody.


RESULTS
Twenty-seven of the 82 patients (33%) were C219-positive in from 1% to 100% of their cells. Thirteen cases (16%) showed a positive reaction in more than 50% of the leukemic cells. Only hyperleukocytosis was significantly associated with higher expression of Pgp. Although 8 of the 13 cases (62%) with more than 50% of cells having Pgp expression were CD34-positive, this association was not statistically significant. A univariate analysis of resistance to induction therapy showed a significantly higher resistance rate in patients with increased Pgp expression (P = 0.01) as well as in those patients with decreased reactivity to myeloperoxidase. The multivariate analysis revealed the independent prognostic value of Pgp expression. C219 reactivity did not have an influence on remission duration.


CONCLUSIONS
Our data indicate that P-glycoprotein expression is a reliable marker of resistance to induction treatment in patients with de novo AML.
Senent
L
L
Hematology Service, La Fe University Hospital, Valencia, Spain.
Jarque
I
I
Martín
G
G
Sempere
A
A
González-García
Y
Y
Gomis
F
F
Pérez-Sirvent
M
M
De La Rubia
J
J
Sanz
M A
MA
D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1 / Q000096:biosynthesis* / Q000276:immunology; D000206:Actuarial Analysis; D000208:Acute Disease; D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000911:Antibodies, Monoclonal / Q000276:immunology; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000494:pharmacology / Q000627:therapeutic use; D002648:Child; D015331:Cohort Studies; D003561:Cytarabine / Q000008:administration & dosage / Q000494:pharmacology; D003630:Daunorubicin / Q000008:administration & dosage / Q000494:pharmacology; D018572:Disease-Free Survival; D018432:Drug Resistance, Multiple; D019008:Drug Resistance, Neoplasm; D005047:Etoposide / Q000008:administration & dosage / Q000494:pharmacology; D005260:Female; D019450:Genes, MDR; D006801:Humans; D007951:Leukemia, Myeloid / Q000188:drug therapy / Q000235:genetics* / Q000401:mortality; D007958:Leukocyte Count; D008297:Male; D008875:Middle Aged; D008942:Mitoxantrone / Q000008:administration & dosage / Q000494:pharmacology; D009363:Neoplasm Proteins / Q000096:biosynthesis* / Q000235:genetics / Q000276:immunology; D014411:Neoplastic Stem Cells / Q000737:chemistry; D011379:Prognosis; D012074:Remission Induction
D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1; D000911:Antibodies, Monoclonal; D009363:Neoplasm Proteins; D003561:Cytarabine; D005047:Etoposide; D008942:Mitoxantrone; D003630:Daunorubicin