P-glycoprotein expression in adult acute myeloid leukemia: correlation with induction treatment outcome.
Drug resistance has become a major cause of the treatment failure in patients with acute leukemia. P-glycoprotein (P-gp), which is associated with multidrug resistance (MDR) phenotype, has been reported to be an important predictor of the treatment outcome. The aim of this study was to analyze the value of P-gp expression in bone marrow cells as a predictor of the response to remission induction chemotherapy, as well as duration of remission in adult patients with newly diagnosed acute myeloid leukemia (AML). We examined the expression of P-gp in 31 patients using the monoclonal antibody UIC2. Direct immunofluorescent labeling was performed and samples were analyzed by flow cytomery. Kolmogorov-Smirnov test (D-value) was used to estimate UIC2 staining. A D > or = 0.3 for labeling of gated leukaemic blasts as compared to that of the isotypic control was defined positive (+) and compared to clinical data. P-gp expression was found in 14/31 (45.6%) patients, 17/31 (54.8%) of the samples were found P-gp negative(-). No correlation was found regarding age, sex and FAB subtype, altough 6/14 (43%) cases with more than 50% of cells having P-gp expression, were CD34+/CD7+. Complete remission rates were significantly lower in UIC2+ patients than in UIC2- cases (70% vs 35%, p < 0.01). Complete remission duration was also shorter in UIC2+ patients (6 vs 12.4 months). Our data indicate, that P-gp expression is a reliable marker of resistance to induction treatment in patients with de novo AML and can help to identify patients who may require alternative regimens designed to overcome therapy resistance.
Tóthová
E
E
Department of Hematology, Medical Faculty Hospital and UPJS, Kosice, Slovak Republic. etothova@post.sk
Elbertová
A
A
Fricová
M
M
Kafková
A
A
Hlebasková
M
M
Svorcová
E
E
Stecová
N
N
Guman
T
T
Raffac
S
S
D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1 / Q000096:biosynthesis*; D000293:Adolescent; D000328:Adult; D000368:Aged; D000911:Antibodies, Monoclonal / Q000378:metabolism; D018952:Antigens, CD34 / Q000096:biosynthesis; D019011:Antigens, CD7 / Q000096:biosynthesis; D005260:Female; D005434:Flow Cytometry; D006801:Humans; D015470:Leukemia, Myeloid, Acute / Q000378:metabolism* / Q000401:mortality* / Q000628:therapy; D008297:Male; D008856:Microscopy, Fluorescence; D008875:Middle Aged; D010641:Phenotype; D013997:Time Factors; D016896:Treatment Outcome
D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1; D000911:Antibodies, Monoclonal; D018952:Antigens, CD34; D019011:Antigens, CD7