title: 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.
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.
authors.affiliation: Department of Hematology, University of Groningen and University Medical Center Groningen, Groningen, The Netherlands.
authors.forename: C
authors.initials: C
authors.lastname: Woolthuis
authors.forename: A
authors.initials: A
authors.lastname: Agool
authors.forename: S
authors.initials: S
authors.lastname: Olthof
authors.forename: R H J A
authors.initials: RH
authors.lastname: Slart
authors.forename: G
authors.initials: G
authors.lastname: Huls
authors.forename: W M
authors.initials: WM
authors.lastname: Smid
authors.forename: J J
authors.initials: JJ
authors.lastname: Schuringa
authors.forename: E
authors.initials: E
authors.lastname: Vellenga
mesh_terms: D000328:Adult; D018952:Antigens, CD34 / Q000378:metabolism; D001853:Bone Marrow / Q000378:metabolism; D002453:Cell Cycle; D003114:Colony-Forming Units Assay; D015224:Dideoxynucleosides / Q000493:pharmacokinetics; D005500:Follow-Up Studies; D055014:Granulocyte-Macrophage Progenitor Cells / Q000166:cytology / Q000378:metabolism; D018380:Hematopoietic Stem Cell Transplantation; D006801:Humans; D008223:Lymphoma / Q000628:therapy; D008875:Middle Aged; D057054:Molecular Imaging / Q000379:methods*; D023461:Myeloid Progenitor Cells / Q000166:cytology / Q000378:metabolism*; D010641:Phenotype; D049268:Positron-Emission Tomography; D019275:Radiopharmaceuticals / Q000493:pharmacokinetics; D014018:Tissue Distribution; D014182:Transplantation, Autologous; D051598:Whole Body Imaging
chemical_list: D018952:Antigens, CD34; D015224:Dideoxynucleosides; D019275:Radiopharmaceuticals; C002854:alovudine