Predictive value for treatment outcome in acute myeloid leukemia of cellular daunorubicin accumulation and P-glycoprotein expression simultaneously determined by flow cytometry

Blood. 1995 Apr 15;85(8):2147-53.

Abstract

To evaluate the clinical relevance of multidrug resistance (MDR) phenotype, the intracellular daunorubicin accumulation (IDA) and P-glycoprotein (P-gp) expression were investigated in 87 adult patients with acute leukemia: 69 patients with de novo acute myeloid leukemia (AML), 10 with AML at relapse, and eight with secondary leukemia to myelodysplastic syndromes (MDS-AML). IDA and P-gp expression were determined by double-labeling flow cytometry analysis. Of 87 patients, 36 expressed P-gp (41%). P-gp expression was more frequently observed in AML at relapse and MDS-AML as compared with de novo AML (P = .0001). P-gp expression was significantly associated with CD34 expression (P = .0003) and chromosome 7 abnormalities (P = .027). A significantly reduced IDA was observed in P-gp+ as compared with P-gp- patients (P = .0007). Of the 87 patients, 51 achieved complete remission (CR). A reduced IDA was observed in patients in failure as compared with patients in CR (22% +/- 17% v 42% +/- 21%; P = 10(-4). Twelve of 36 P-gp+ patients as compared with 40 of 51 P-gp- patients achieved CR (33% v 78%; P = 10(-4). The prognostic value of IDA and P-gp expression was confirmed in multivariate analysis. These data suggest that the determination of IDA and P-gp expression may be useful in designing therapy for patients with AML.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • ATP Binding Cassette Transporter, Subfamily B, Member 1 / analysis*
  • ATP Binding Cassette Transporter, Subfamily B, Member 1 / genetics
  • Acute Disease
  • Adolescent
  • Adult
  • Aged
  • Antigens, CD / analysis
  • Antigens, CD34
  • Antineoplastic Combined Chemotherapy Protocols / therapeutic use
  • Blast Crisis / blood
  • Blast Crisis / drug therapy
  • Blast Crisis / genetics
  • Blast Crisis / mortality
  • Blast Crisis / pathology
  • Blood Cell Count
  • Bone Marrow / chemistry*
  • Bone Marrow / pathology
  • Chromosome Deletion
  • Chromosomes, Human, Pair 7 / ultrastructure
  • Cytarabine / administration & dosage
  • Daunorubicin / administration & dosage
  • Daunorubicin / analogs & derivatives
  • Daunorubicin / pharmacokinetics*
  • Drug Resistance, Multiple
  • Female
  • Flow Cytometry*
  • Gene Expression
  • Humans
  • Idarubicin / administration & dosage
  • Karyotyping
  • Leukemia, Myeloid / blood
  • Leukemia, Myeloid / drug therapy*
  • Leukemia, Myeloid / genetics
  • Leukemia, Myeloid / mortality
  • Leukemia, Myeloid / pathology
  • Male
  • Middle Aged
  • Mitoxantrone / administration & dosage
  • Monosomy
  • Myelodysplastic Syndromes / pathology
  • Neoplasm Proteins / analysis*
  • Neoplasm Proteins / genetics
  • Neoplasm Recurrence, Local
  • Neoplastic Stem Cells / chemistry*
  • Prognosis
  • Prospective Studies
  • Quinine / administration & dosage
  • Remission Induction
  • Risk
  • Salvage Therapy
  • Treatment Outcome

Substances

  • ATP Binding Cassette Transporter, Subfamily B, Member 1
  • Antigens, CD
  • Antigens, CD34
  • Neoplasm Proteins
  • Cytarabine
  • Quinine
  • Mitoxantrone
  • zorubicin
  • Idarubicin
  • Daunorubicin