CD34+ leukemic subpopulation predominantly displays lower spontaneous apoptosis and has higher expression levels of Bcl-2 and MDR1 genes than CD34- cells in childhood AML

Ann Hematol. 2008 May;87(5):353-60. doi: 10.1007/s00277-008-0439-2. Epub 2008 Jan 29.

Abstract

In view of obscure clinical and biological significance of leukemic cells heterogeneity, we studied the efficacy of apoptosis, proliferation, and expression levels of the Bcl-2, MDR1, LRP, and BCRP genes in sorted CD34+ and CD34- subpopulations of childhood AML leukemic samples. In five out of nine cases, CD34+ cells were less sensitive to spontaneous apoptosis and had from 1.2- to 5.0-fold higher expression levels of Bcl-2 (eight of ten) and from 1.5- to 28.7-fold higher expression levels of MDR1 (eight of ten). The expression levels of the LRP gene were from 1.1- to 1.8-fold higher in CD34+ subpopulations (five of ten cases), and the expression levels of the BCRP gene were from 1.1- to 22.4-fold higher in CD34+ leukemic cells (six of ten). In all M4 cases, the expression levels of LRP were higher in the CD34- subpopulation. Significant differences in the patterns of genes expression between patients do not allow us to conclude that the CD34+ fractions have more resistant phenotype than the CD34- subpopulations. Nevertheless, distinctions between CD34+ and CD34- cells may lead to different chemosensitivities between leukemic subpopulations in vivo and may determine the alteration of the leukemic immunophenotype during treatment and in relapse.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • ATP Binding Cassette Transporter, Subfamily B, Member 1 / metabolism*
  • ATP Binding Cassette Transporter, Subfamily G, Member 2
  • ATP-Binding Cassette Transporters / metabolism
  • Antigens, CD34*
  • Apoptosis / drug effects
  • Apoptosis / physiology*
  • Child
  • Child, Preschool
  • Cohort Studies
  • Gene Expression Profiling
  • Humans
  • Leukemia, Myeloid, Acute* / classification
  • Leukemia, Myeloid, Acute* / genetics
  • Leukemia, Myeloid, Acute* / immunology
  • Leukemia, Myeloid, Acute* / physiopathology
  • Lymphocyte Subsets / classification
  • Lymphocyte Subsets / metabolism*
  • Neoplasm Proteins / metabolism
  • Neoplasm, Residual / metabolism
  • Neoplasm, Residual / physiopathology
  • Proto-Oncogene Proteins c-bcl-2 / metabolism*
  • Recurrence
  • 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
  • Antigens, CD34
  • Neoplasm Proteins
  • Proto-Oncogene Proteins c-bcl-2
  • Vault Ribonucleoprotein Particles
  • major vault protein