Multiple drug resistance mediated by P-glycoprotein is not a major factor in a slow response to therapy in childhood ALL

Pediatr Hematol Oncol. 1998 Jan-Feb;15(1):11-21. doi: 10.3109/08880019809009504.

Abstract

In childhood acute lymphoblastic leukemia (ALL), early response to treatment is an important prognostic factor and drug resistance is a major cause of poor outcome. One of the most investigated resistance mechanisms is P-glycoprotein (P-gp)-mediated multiple drug resistance (MDR). We analyzed P-gp using flow cytometry with monoclonal antibody JSB1 in a series of 118 children with ALL, 103 at diagnosis and 15 at relapse. Increased P-gp expression was found in 55 (53%) patients at diagnosis and in 11 (73%) at relapse. We also analyzed the bone marrow aspirate slides for early response to treatment in a central review. No correlation was found between P-gp and early response. Patients with T-ALL had higher P-gp levels than the others, 5.3% versus 1.0% (P = .002). We conclude that P-gp-mediated multiple drug resistance is not a factor in a slow response to ALL induction therapy.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • ATP Binding Cassette Transporter, Subfamily B, Member 1 / biosynthesis*
  • Adolescent
  • Antineoplastic Combined Chemotherapy Protocols / therapeutic use*
  • Asparaginase / administration & dosage
  • Blast Crisis
  • Bone Marrow / pathology
  • Burkitt Lymphoma / drug therapy*
  • Burkitt Lymphoma / pathology
  • Burkitt Lymphoma / physiopathology*
  • Child
  • Child, Preschool
  • Cyclophosphamide / administration & dosage
  • Cytarabine / administration & dosage
  • Doxorubicin / administration & dosage
  • Drug Resistance, Multiple*
  • Finland
  • Follow-Up Studies
  • Humans
  • Infant
  • Leukemia-Lymphoma, Adult T-Cell / drug therapy*
  • Leukemia-Lymphoma, Adult T-Cell / pathology
  • Leukemia-Lymphoma, Adult T-Cell / physiopathology
  • Mercaptopurine / administration & dosage
  • Methotrexate / administration & dosage
  • Predictive Value of Tests
  • Prednisone / administration & dosage
  • Prognosis
  • Recurrence
  • Remission Induction
  • Vincristine / administration & dosage

Substances

  • ATP Binding Cassette Transporter, Subfamily B, Member 1
  • Cytarabine
  • Vincristine
  • Doxorubicin
  • Cyclophosphamide
  • Mercaptopurine
  • Asparaginase
  • Prednisone
  • Methotrexate