title: Coexpression of Multiple ABC-Transporters is Strongly Associated with Treatment Response in Childhood Acute Myeloid Leukemia.
abstract: BACKGROUND
  To analyze whether expression of ABC-transporters is associated with remission rate and long-term outcome in a prospective clinical trial of childhood acute myeloid leukemia (AML).
  
  
  METHODS
  The expression of four ABC-transporter genes (ABCA3 encoding drug transporter ABCA3, ABCB1 encoding multidrug resistance protein 1, ABCC3 encoding multidrug resistance-associated protein 3, and ABCG2 encoding breast cancer resistance protein) was measured by TaqMan real time polymerase chain reaction in pretreatment samples from 112 children with AML. Patients were treated according to multicenter study AML-Berlin, Frankfurt, Munich (BFM) 2004.
  
  
  RESULTS
  ABCC3 (P = 0.009) and ABCG2 (P = 0.03) were associated with a lower chance to achieve remission after the first course of chemotherapy. ABCC3 was associated with lower relapse free survival (RFS) (P = 0.02). ABCG2 was expressed at higher levels in subtypes of AML with favorable outcome but within standard- and high-risk patients, it was associated with poor outcome (P = 0.02). A strong association was observed between the number of overexpressed ABC-transporters and the chance to achieve remission (P = 0.01) or the chance of RFS (P < 0.001).
  
  
  CONCLUSIONS
  The intensive treatment regimen of AML-BFM 2004 did not readily overcome drug resistance caused by ABC-transporters. Inhibition of ABC-transporters might be particularly useful in patients who express multiple of these genes.
authors.affiliation: University of Ulm, Children's Hospital, Ulm, Germany.
authors.forename: Stephan
authors.initials: S
authors.lastname: Bartholomae
authors.affiliation: Jena University Hospital, Department of Pediatrics, Jena, Germany.
authors.forename: Bernd
authors.initials: B
authors.lastname: Gruhn
authors.affiliation: University of Ulm, Children's Hospital, Ulm, Germany.
authors.forename: Klaus-Michael
authors.initials: KM
authors.lastname: Debatin
authors.affiliation: Medical School Hannover, Children's Hospital, Hannover, Germany.
authors.forename: Martin
authors.initials: M
authors.lastname: Zimmermann
authors.affiliation: Medical School Hannover, Children's Hospital, Hannover, Germany.
authors.forename: Ursula
authors.initials: U
authors.lastname: Creutzig
authors.affiliation: Medical School Hannover, Children's Hospital, Hannover, Germany.
authors.forename: Dirk
authors.initials: D
authors.lastname: Reinhardt
authors.affiliation: University of Ulm, Children's Hospital, Ulm, Germany.
authors.forename: Daniel
authors.initials: D
authors.lastname: Steinbach
mesh_terms: D018528:ATP-Binding Cassette Transporters / Q000096:biosynthesis* / Q000235:genetics; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D002648:Child; D018572:Disease-Free Survival; D005260:Female; D006801:Humans; D015470:Leukemia, Myeloid, Acute / Q000188:drug therapy* / Q000235:genetics / Q000401:mortality; D008297:Male; D011446:Prospective Studies; D060888:Real-Time Polymerase Chain Reaction; D016896:Treatment Outcome
chemical_list: D018528:ATP-Binding Cassette Transporters
keywords: breast cancer resistance protein; multidrug resistance gene; multidrug resistance-associated protein; pediatric AML; risk group