Chemotherapy-induced alteration of SDF-1/CXCR4 expression in bone marrow-derived mesenchymal stem cells from adolescents and young adults with acute lymphoblastic leukemia

J Pediatr Hematol Oncol. 2014 Nov;36(8):617-23. doi: 10.1097/MPH.0000000000000220.

Abstract

Bone marrow-derived mesenchymal stem cells (BM-MSCs) in the marrow stroma provide a scaffold for hematopoiesis. Chemokine stromal cell-derived factor-1 (SDF-1) and its receptor CXCR4 have been shown to affect the engraftment of hematopoietic stem cells. However, little is known about SDF-1/CXCR4's functions in regulating BM-MSCs in humans. As an initial step toward this issue, we have evaluated expression of SDF-1/CXCR4 in the BM-MSCs from a cohort of adolescents and young adults with acute lymphoblastic leukemia (ALL). We found a decrease of the CXCR4 level and an increase of the SDF-1 level in these MSCs of ALL. Moreover, cell migration appeared to be impaired in the MSCs of ALL. These changes were reversed by chemotherapy. Taken together, alteration of SDF-1/CXCR4 expression could be potentially developed as biomarkers for monitoring the effectiveness of chemotherapy.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Antineoplastic Combined Chemotherapy Protocols / administration & dosage*
  • Bone Marrow Cells / drug effects
  • Bone Marrow Cells / physiology
  • Cell Differentiation / drug effects
  • Cell Differentiation / physiology
  • Cell Movement / drug effects
  • Cell Movement / physiology
  • Cells, Cultured
  • Chemokine CXCL12 / genetics*
  • Chemokine CXCL12 / metabolism
  • Dipeptidyl Peptidase 4 / genetics
  • Dipeptidyl Peptidase 4 / metabolism
  • Drug Monitoring / methods*
  • Gene Expression / drug effects
  • Hematopoiesis / drug effects
  • Hematopoiesis / physiology
  • Humans
  • Mesenchymal Stem Cells / drug effects*
  • Mesenchymal Stem Cells / physiology
  • Precursor Cell Lymphoblastic Leukemia-Lymphoma / drug therapy*
  • Precursor Cell Lymphoblastic Leukemia-Lymphoma / metabolism
  • Receptors, CXCR4 / genetics*
  • Receptors, CXCR4 / metabolism
  • Young Adult

Substances

  • CXCL12 protein, human
  • CXCR4 protein, human
  • Chemokine CXCL12
  • Receptors, CXCR4
  • DPP4 protein, human
  • Dipeptidyl Peptidase 4