Expression of MDR1, LRP, BCRP and Bcl-2 genes at diagnosis of childhood all: comparison with MRD status after induction therapy

Exp Oncol. 2008 Sep;30(3):248-52.

Abstract

Aim: to investigate properties of leukemic cells by sorting out children diagnosed with ALL with different response to chemotherapy based on MRD level.

Methods: We used a minimal residual disease (MRD) data on day 36 obtained with 3-colour flow cytometry as a reference. In view of MRD results, we used real-time PCR to assess expression levels of multidrug resistance associated genes MDR1, LRP and BCRP, antiapoptotic gene Bcl-2 in initial samples from children diagnosed with ALL. P-gp expression and function in initial samples were analyzed by flow cytometry.

Results: Briefly, medians of relative expression levels of MDR1 gene were roughly comparable and in MRD(+) group came to 22.8 (0.02-26.6; n = 9) vs 24.8 (3.9-41.4; n = 10) in MRD(-) group. Bcl-2 gene showed tendency to higher expression levels in MRD(+) group with median at 5992.9 (521.0-10362.0; n = 9) compared to 3183.6 (1947.9-6581.0; n = 10) in MRD(-) group. LRP gene relative expression levels were similar in both groups and came to 1934.9 (1500.7-3490.4; n = 9) and 1408.5 (665.5-2917.1; n = 10) in MRD + and MRD(-) groups, respectively. The median of BCRP expression levels in MRD + group was considerably lower than that in MRD - group, namely 76000.0 (48196.2-169230.8; n = 9) and 227967.2 (16683.7-422222.2; n = 10), respectively, but statistical analysis showed no significant difference for this parameter.

Conclusion: We investigated expression of multidrug resistance genes MDR1, LRP and BCRP and antiapoptotic gene Bcl-2 in leukemic cells at diagnosis, and MRD level at the end of induction therapy, and could not find obvious relations between these parameters.

MeSH terms

  • ATP Binding Cassette Transporter, Subfamily B
  • 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
  • Adolescent
  • Child
  • Child, Preschool
  • Drug Resistance, Multiple
  • Flow Cytometry
  • Gene Expression Regulation, Neoplastic
  • Humans
  • Infant
  • Lymphoma, B-Cell / genetics
  • Lymphoma, B-Cell / pathology
  • Neoadjuvant Therapy
  • Neoplasm Proteins / genetics*
  • Neoplasm Proteins / metabolism
  • Neoplasm, Residual / genetics
  • Precursor Cell Lymphoblastic Leukemia-Lymphoma / genetics*
  • Precursor Cell Lymphoblastic Leukemia-Lymphoma / pathology
  • Prognosis
  • Proto-Oncogene Proteins c-bcl-2 / genetics*
  • Proto-Oncogene Proteins c-bcl-2 / metabolism
  • RNA, Messenger / genetics
  • RNA, Messenger / metabolism
  • RNA, Neoplasm / genetics
  • RNA, Neoplasm / metabolism
  • Remission Induction
  • Reverse Transcriptase Polymerase Chain Reaction
  • Vault Ribonucleoprotein Particles / genetics*
  • Vault Ribonucleoprotein Particles / metabolism

Substances

  • ABCB1 protein, human
  • ABCG2 protein, human
  • ATP Binding Cassette Transporter, Subfamily B
  • ATP Binding Cassette Transporter, Subfamily B, Member 1
  • ATP Binding Cassette Transporter, Subfamily G, Member 2
  • ATP-Binding Cassette Transporters
  • Neoplasm Proteins
  • Proto-Oncogene Proteins c-bcl-2
  • RNA, Messenger
  • RNA, Neoplasm
  • Vault Ribonucleoprotein Particles
  • major vault protein