title: Expression of multidrug resistance-associated proteins predicts prognosis in childhood and adult acute lymphoblastic leukemia.
abstract: OBJECTIVE
  Patients with acute lymphoblastic leukemia (ALL) are treated with a variety of chemotherapeutic drugs, which can be transported by six multidrug resistance-associated proteins (MRP). These MRPs have strongly overlapping functional activities. The aim of this study was to investigate the expression levels of MRP1 to MRP6 and study their effect on prognosis.
  
  
  METHODS
  The mRNA expression levels of MRP1 to MRP6 were analyzed by quantitative real-time PCR in leukemic blasts of 105 de novo ALL patients (adults, n=49; children, n=56) including 70% B-lineage and 30% T-lineage ALL patients.
  
  
  RESULTS
  Adults showed a higher expressions of MRP1 (P=0.008), MRP2 (P=0.026), and MRP3 (P=0.039) than children. Interestingly, this difference disappeared when patients were categorized based on clinical outcome. Relapsed patients showed a higher expression of all MRP genes, except MRP4. For the total group of ALL patients, the expressions of MRP1, MRP2, MRP3, MRP5, and MRP6 predicted relapse. Moreover, high expression of all MRP genes, except MRP4, was associated with a reduced relapse-free survival in children and adults (MRP1, P=0.005; MRP2, P=0.008; MRP3, P=0.001; MRP5, P=0.016; MRP6, P=0.037).
  
  
  CONCLUSIONS
  The present study shows that a subset of ALL patients with high MRP expression has an unfavorable prognosis independently of age.
authors.affiliation: Department of Pediatric Oncology and Hematology, University Medical Center Groningen, Groningen, the Netherlands.
authors.forename: Sabine L A
authors.initials: SL
authors.lastname: Plasschaert
authors.forename: Eveline S J M
authors.initials: ES
authors.lastname: de Bont
authors.forename: Marike
authors.initials: M
authors.lastname: Boezen
authors.forename: Dorina M
authors.initials: DM
authors.lastname: vander Kolk
authors.forename: Simon M J G
authors.initials: SM
authors.lastname: Daenen
authors.forename: Klaas Nico
authors.initials: KN
authors.lastname: Faber
authors.forename: Willem A
authors.initials: WA
authors.lastname: Kamps
authors.forename: Elisabeth G E
authors.initials: EG
authors.lastname: de Vries
authors.forename: Edo
authors.initials: E
authors.lastname: Vellenga
mesh_terms: D000328:Adult; D002648:Child; D005260:Female; D015870:Gene Expression; D006801:Humans; D008297:Male; D027425:ATP-Binding Cassette, Sub-Family C Proteins / Q000235:genetics* / Q000378:metabolism; D054198:Precursor Cell Lymphoblastic Leukemia-Lymphoma / Q000175:diagnosis* / Q000235:genetics / Q000401:mortality; D011379:Prognosis; D012333:RNA, Messenger / Q000032:analysis / Q000378:metabolism; D012334:RNA, Neoplasm / Q000737:chemistry; D012008:Recurrence
chemical_list: D027425:ATP-Binding Cassette, Sub-Family C Proteins; D012333:RNA, Messenger; D012334:RNA, Neoplasm