Auto-SCT induces a phenotypic shift from CMP to GMP progenitors, reduces clonogenic potential and enhances in vitro and in vivo cycling activity defined by (18)F-FLT PET scanning

Bone Marrow Transplant. 2011 Jan;46(1):110-5. doi: 10.1038/bmt.2010.75. Epub 2010 Apr 12.

Abstract

Autologous SCT (auto-SCT) introduces a reduced tolerance to chemotherapy even in patients with adequate engraftment, suggesting long-term effects of the transplantation procedure on the BM capacity. To study the hematopoietic cell compartment after auto-SCT, CD34(+) BM cells (n = 16) from patients at 6-9 months after auto-SCT were studied with regard to the progenitor subsets, colony frequency and cell cycle status. The BM compartments were studied in vivo using PET tracer 3-fluoro-3-deoxy-L-thymidine (¹⁸F-FLT PET). BM CD34(+) cells after auto-SCT were compared with normal CD34(+) cells and showed a phenotypic shift from common myeloid progenitor (CMP mean percentage 3.7 vs 19.4%, P=0.001) to granulocyte-macrophage progenitor (GMP mean percentage 51.8 vs 27.6%, P=0.01). In addition, a reduced clonogenic potential and higher cycling activity especially of the GMP fraction (41% ± 4 in G2/S phase vs 19% ± 2, P = 0.03) were observed in BM after auto-SCT compared with normal. The enhanced cycling activity was confirmed in vivo by showing a significantly higher uptake of the ¹⁸F-FLT PET tracer by the BM compartment. This study shows that auto-SCT results in defects of the hematopoietic compartment at least 6 months after auto-SCT, characterized by changes in the composition of progenitor subsets and enhanced in vitro and in vivo cycling activity.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Antigens, CD34 / metabolism
  • Bone Marrow / metabolism
  • Cell Cycle*
  • Colony-Forming Units Assay
  • Dideoxynucleosides / pharmacokinetics
  • Follow-Up Studies
  • Granulocyte-Macrophage Progenitor Cells / cytology
  • Granulocyte-Macrophage Progenitor Cells / metabolism
  • Hematopoietic Stem Cell Transplantation*
  • Humans
  • Lymphoma / therapy
  • Middle Aged
  • Molecular Imaging / methods*
  • Myeloid Progenitor Cells / cytology
  • Myeloid Progenitor Cells / metabolism*
  • Phenotype*
  • Positron-Emission Tomography
  • Radiopharmaceuticals / pharmacokinetics
  • Tissue Distribution
  • Transplantation, Autologous
  • Whole Body Imaging

Substances

  • Antigens, CD34
  • Dideoxynucleosides
  • Radiopharmaceuticals
  • alovudine