Multidrug resistance (MDR-1) expression in AIDS-related lymphomas

Leuk Res. 2002 Feb;26(2):121-7. doi: 10.1016/s0145-2126(01)00113-8.

Abstract

P-glycoprotein is a product of the multidrug resistance (MDR-1) gene. In non-Hodgkin's lymphoma, less than 20% of untreated de novo lymphomas express MDR-1 compared with approximately 50% after failure of chemotherapy. We wished to study the expression of MDR-1 in AIDS-related non-Hodgkin's lymphoma (AIDS-NHL). Tissue biopsies from 50 patients with newly diagnosed AIDS-NHL were studied by immunohistochemical analysis using C494, a monoclonal antibody specific for the MDR-1 isoform of P-gp. MDR-1 expression was correlated with patient demographics, lymphoma characteristics, response to chemotherapy, and survival. Forty-six males and four females with a median age of 38 years (range 26-63) were studied. A prior AIDS-defining opportunistic infection was reported in 35 patients (70%). The median CD4+ lymphocyte count was 69/mm(3) (range 0-920). Thirty-two patients (63%) had received prior anti-HIV therapy, including a protease inhibitor in five (10%). Pathologic types consisted of diffuse large cell in 13 (26%), immunoblastic in 13 (26%), small non-cleaved in 22 (44%), and high grade not otherwise specified in two (4%). The majority of patients (76%) had stage III/IV disease. Pre-treatment lymphoma tissues from 33 patients (66%) stained positively for MDR-1. MDR-1 positive patients had a significantly lower complete remission rate compared to MDR-1 negative patients (33 versus 65%, P=0.042). Duration of complete response was significantly longer in MDR-1 negative patients compared with MDR-1 positive patients (not reached versus 9.9 months, P=0.003). Strategies to overcome MDR-1 expression may be important for initial treatment in patients with AIDS-NHL.

Publication types

  • Comparative Study

MeSH terms

  • ATP Binding Cassette Transporter, Subfamily B, Member 1 / biosynthesis*
  • ATP Binding Cassette Transporter, Subfamily B, Member 1 / genetics
  • Acquired Immunodeficiency Syndrome / mortality
  • Adult
  • Anti-HIV Agents / therapeutic use
  • Antineoplastic Combined Chemotherapy Protocols / administration & dosage
  • Antineoplastic Combined Chemotherapy Protocols / metabolism*
  • Antineoplastic Combined Chemotherapy Protocols / pharmacology
  • Antineoplastic Combined Chemotherapy Protocols / therapeutic use
  • Bleomycin / administration & dosage
  • Bleomycin / metabolism
  • Bleomycin / pharmacology
  • Cyclophosphamide / administration & dosage
  • Cyclophosphamide / metabolism
  • Cyclophosphamide / pharmacology
  • Dexamethasone / administration & dosage
  • Dexamethasone / metabolism
  • Dexamethasone / pharmacology
  • Disease-Free Survival
  • Doxorubicin / administration & dosage
  • Doxorubicin / metabolism
  • Doxorubicin / pharmacology
  • Drug Resistance, Multiple / genetics*
  • Drug Resistance, Neoplasm / genetics*
  • Female
  • Gene Expression Regulation, Leukemic*
  • Humans
  • Leucovorin / administration & dosage
  • Leucovorin / metabolism
  • Leucovorin / pharmacology
  • Lymphoma, AIDS-Related / drug therapy
  • Lymphoma, AIDS-Related / genetics
  • Lymphoma, AIDS-Related / metabolism*
  • Lymphoma, AIDS-Related / mortality
  • Male
  • Methotrexate / administration & dosage
  • Methotrexate / metabolism
  • Methotrexate / pharmacology
  • Middle Aged
  • Neoplasm Proteins / biosynthesis*
  • Neoplasm Proteins / genetics
  • Prednisone / administration & dosage
  • Prednisone / metabolism
  • Prednisone / pharmacology
  • Remission Induction
  • Retrospective Studies
  • Survival Analysis
  • Vincristine / administration & dosage
  • Vincristine / metabolism
  • Vincristine / pharmacology

Substances

  • ATP Binding Cassette Transporter, Subfamily B, Member 1
  • Anti-HIV Agents
  • Neoplasm Proteins
  • Bleomycin
  • Vincristine
  • Dexamethasone
  • Doxorubicin
  • Cyclophosphamide
  • Leucovorin
  • Prednisone
  • Methotrexate

Supplementary concepts

  • CHOP protocol
  • M-BACOD protocol