title: P-glycoprotein expression on acute myeloid leukaemia blast cells at diagnosis predicts response to chemotherapy and survival.
abstract: P-glycoprotein (Pgp) expression, which is associated with the multi-drug resistance (MDR) phenotype, has been reported to be a useful predictor of treatment outcome in acute leukaemia. We have examined the expression of Pgp on acute myeloid leukaemia (AML) cells in 54 newly diagnosed patients, using a novel streptavidin-biotin complex (ABC) technique. 55% of patients at diagnosis were positive for Pgp with JSB-1, a monoclonal antibody that binds to an internal epitope of Pgp. All patients received intensive induction chemotherapy. Post-remission treatment consisted of further chemotherapy +/- bone marrow transplantation. Complete remission (CR) rates were significantly lower in the Pgp positive group than in the Pgp negative group (60% v 92%; P = 0.02). The overall survival for Pgp-positive patients was significantly shorter (329 v 534d, P = 0.004), disease-free survival was also reduced but the difference was not statistically significant (median 277 v 522d, P = 0.16). In this study CD34 expression was not predictive of response to chemotherapy nor was it associated with Pgp expression. Our results confirm the prognostic value of Pgp expression in AML at diagnosis and we suggest that Pgp could be a useful therapeutic target for reversing multi-drug resistance. Furthermore, our simple and sensitive method of detecting Pgp should enable widespread testing to be performed.
authors.affiliation: University Department of Haematology, Manchester Royal Infirmary.
authors.forename: P
authors.initials: P
authors.lastname: Wood
authors.forename: R
authors.initials: R
authors.lastname: Burgess
authors.forename: A
authors.initials: A
authors.lastname: MacGregor
authors.forename: J A
authors.initials: JA
authors.lastname: Yin
mesh_terms: D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1 / Q000378:metabolism*; D000328:Adult; D000368:Aged; D018432:Drug Resistance, Multiple; D005260:Female; D006801:Humans; D015470:Leukemia, Myeloid, Acute / Q000188:drug therapy / Q000378:metabolism* / Q000401:mortality; D007958:Leukocyte Count; D008297:Male; D008875:Middle Aged; D011379:Prognosis; D016019:Survival Analysis
chemical_list: D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1