The biological behavior of SDF-1/CXCR4 in patients with myelodysplastic syndrome

Med Oncol. 2012 Jun;29(2):1202-8. doi: 10.1007/s12032-011-9943-7. Epub 2011 May 10.

Abstract

The purpose of this investigation is to evaluate the biological behavior of stromal cell-derived factor-l (SDF-1) in migration, adhesion, and apoptosis as well as the related signaling transduction pathways in patients with myelodysplastic syndrome (MDS) and acute myeloid leukemia (AML). We chose 22 patients with MDS, 7 patients with de novo AML, and 8 patients with non-clonal cytopenia diseases. We performed flow cytometric analysis of CD34(+) cells apoptosis using annexinV-FITC, which binds to exposed phosphatidylserine on apoptotic cells. The cell adhesion capability was detected by CCK-8 assay. The migration ability of the cell was checked by transwell assay. Furthermore, we measured SDF-1 levels in BM plasma from patients by enzyme-linked immunosorbent assay (ELISA). Our results indicated that the apoptosis of CD34(+) cell was significantly increased in the Low-grade MDS (IPSS score ≤ 1.0) patients compared with the high-grade MDS (IPSS score ≥ 1.5) (21.33% vs. 7.27%, P < 0.001) and patients with de novo AML (21.33% vs. 7.53%, P < 0.001). SDF-1 promoted CXCR4 high expression cells adhesion to the stroma cells (MSC) and induced these cells migration. SDF-1 could trigger the occurrence of polarized morphology of the cells that expressed CXCR4 high. After addition of wortmannin or PTX, the ability of adhesion and migration of the cells that expressed CXCR4 high decreased. But in the patient's cells that expressed CXCR4 low, there was no above-mentioned phenomenon. So we can suppose that the signaling pathway of SDF-1/CXCR4 axis is PI3K pathway, and we should do more things about this pathway and may find out the target treatment of MDS.

Publication types

  • Comparative Study

MeSH terms

  • Apoptosis
  • Bone Marrow / metabolism
  • Bone Marrow / pathology
  • Case-Control Studies
  • Cell Adhesion
  • Cell Movement*
  • Chemokine CXCL12 / metabolism*
  • Enzyme-Linked Immunosorbent Assay
  • Flow Cytometry
  • Humans
  • Myelodysplastic Syndromes / metabolism*
  • Myelodysplastic Syndromes / pathology*
  • Neoplasm Grading
  • Phosphatidylinositol 3-Kinases / metabolism
  • Receptors, CXCR4 / metabolism*
  • Signal Transduction
  • Stromal Cells / metabolism
  • Stromal Cells / pathology
  • Tumor Cells, Cultured

Substances

  • CXCL12 protein, human
  • CXCR4 protein, human
  • Chemokine CXCL12
  • Receptors, CXCR4
  • Phosphatidylinositol 3-Kinases