Increased expression of the breast cancer resistance protein (BCRP) in relapsed or refractory acute myeloid leukemia (AML)

Leukemia. 2002 May;16(5):833-9. doi: 10.1038/sj.leu.2402496.

Abstract

Expression of the multidrug resistance proteins P-glycoprotein, encoded by the MDR1 gene, multidrug resistance-associated protein (MRP1) and the lung resistance-related protein or major vault protein (LRP/MVP) is associated with clinical resistance to chemotherapy in acute myeloid leukemia (AML). Recently, the breast cancer-resistant protein (BCRP), the equivalent of mitoxantrone-resistant protein (MXR) or placental ABC transporter (ABCP), was described in AML. We investigated MDR1, MRP1, LRP/MVP and BCRP mRNA expression simultaneously in 20 paired clinical AML samples from diagnosis and relapse or refractory disease, using quantitative Taqman analysis. In addition, standard assays for P-glycoprotein expression and function were performed. BCRP was the only resistance protein that was expressed at a significantly higher RNA level (median 1.7-fold, P = 0.04) at relapsed/refractory state as compared to diagnosis. In contrast, LRP/MVP mRNA expression decreased as disease evolved (P = 0.02), whereas MDR1 and MRP1 mRNA levels were not different at relapse as compared to diagnosis. Also, at the protein level no difference of MDR1 between diagnosis and relapse was found. A significant co-expression of BCRP and MDR1 was found at diagnosis (r = 0.47, P = 0.04). The present results suggest that BCRP, but not MDR1, MRP1 or LRP/MVP is associated with clinical resistant disease in AML.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • ATP Binding Cassette Transporter, Subfamily B, Member 1 / genetics
  • ATP Binding Cassette Transporter, Subfamily B, Member 1 / metabolism
  • ATP Binding Cassette Transporter, Subfamily G, Member 2
  • ATP-Binding Cassette Transporters / genetics
  • ATP-Binding Cassette Transporters / metabolism*
  • ATP-Binding Cassette Transporters / physiology
  • Acute Disease
  • Adolescent
  • Adult
  • Aged
  • Bone Marrow Cells / pathology
  • Child
  • Child, Preschool
  • Disease Progression
  • Drug Resistance, Neoplasm*
  • Humans
  • Infant
  • Leukemia, Myeloid / drug therapy
  • Leukemia, Myeloid / metabolism*
  • Leukemia, Myeloid / pathology
  • Middle Aged
  • Multidrug Resistance-Associated Proteins / genetics
  • Multidrug Resistance-Associated Proteins / metabolism
  • Neoplasm Proteins / genetics
  • Neoplasm Proteins / metabolism*
  • Neoplasm Proteins / physiology
  • Polymerase Chain Reaction
  • RNA, Messenger / metabolism
  • Recurrence
  • Up-Regulation
  • Vault Ribonucleoprotein Particles / genetics
  • Vault Ribonucleoprotein Particles / metabolism

Substances

  • ABCG2 protein, human
  • ATP Binding Cassette Transporter, Subfamily B, Member 1
  • ATP Binding Cassette Transporter, Subfamily G, Member 2
  • ATP-Binding Cassette Transporters
  • Multidrug Resistance-Associated Proteins
  • Neoplasm Proteins
  • RNA, Messenger
  • Vault Ribonucleoprotein Particles
  • major vault protein
  • multidrug resistance-associated protein 1