Enrichment of N-Cadherin and Tie2-bearing CD34+/CD38-/CD123+ leukemic stem cells by chemotherapy-resistance

Cancer Lett. 2010 Oct 1;296(1):65-73. doi: 10.1016/j.canlet.2010.03.021. Epub 2010 May 4.

Abstract

Acute myeloid leukemia (AML) arises from genetic changes at the level of stem cell, various mutations have been elucidated, including AML1-ETO fusion gene has been shown as the representative target of cellular transformation for LSCs originating from hematopoietic stem cells (HSCs) compartment. LSCs resemble HSCs with respect to self-renewal capacity and chemotherapy-resistance. However, LSCs possess specific cell-surface markers, they are proposed to reside within the CD34(+)/CD38(-)/CD123(+) compartment. And the interaction mediated by adhesion molecules between LSCs and niche played a role in chemoresistance of LSCs. Therefore, study on the LSCs surface makers related to niche is helpful for the potential target therapy in the future. In this study, the proportions of CD34(+)/CD38(-)/CD123(+) LSCs compartment co-expressing the three adhesion molecules, N-Cadherin, Tie2 and CD44, respectively, from AML patients before and after chemotherapy were analyzed. We demonstrated N-Cadherin and Tie2 positive CD34(+)/CD38(-)/CD123(+) LSCs populations could be enriched by chemotherapy. Furthermore, AML1/ETO fusion signals and MDR1 expression were detected on the CD34(+)/CD38(-)/CD123(+) LSCs populations expressing N-Cadherin and Tie2. Therefore, N-Cadherin and Tie2 are probably the potential markers for identification of LSCs.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • ADP-ribosyl Cyclase 1 / genetics
  • Adolescent
  • Adult
  • Antigens, CD34 / genetics*
  • Cadherins / genetics*
  • DNA Primers
  • DNA, Complementary / genetics
  • DNA, Neoplasm / genetics
  • Female
  • Flow Cytometry
  • Harringtonines / therapeutic use
  • Homoharringtonine
  • Humans
  • Hyaluronan Receptors / genetics
  • In Situ Hybridization, Fluorescence
  • Interleukin-3 Receptor alpha Subunit / genetics
  • Leukemia, Myeloid, Acute / drug therapy
  • Leukemia, Myeloid, Acute / genetics*
  • Leukemia, Myeloid, Acute / immunology
  • Leukemia, Myeloid, Acute / pathology
  • Male
  • Middle Aged
  • Prognosis
  • RNA, Neoplasm / genetics
  • Receptor, TIE-2 / genetics*
  • Reverse Transcriptase Polymerase Chain Reaction
  • Stem Cells / immunology
  • Stem Cells / metabolism
  • Stem Cells / pathology*

Substances

  • Antigens, CD34
  • CD44 protein, human
  • Cadherins
  • DNA Primers
  • DNA, Complementary
  • DNA, Neoplasm
  • Harringtonines
  • Hyaluronan Receptors
  • Interleukin-3 Receptor alpha Subunit
  • RNA, Neoplasm
  • Homoharringtonine
  • Receptor, TIE-2
  • ADP-ribosyl Cyclase 1