Myeloid differentiation and maturation of SCF+IL-3+IL-11 expanded AC133+/CD34+ cells selected from high-risk breast cancer patients

Neoplasma. 2000;47(2):73-80.

Abstract

The AC133 antigen is selectively expressed on subset of CD 34+ cells isolated from leukapheresis products from high risk breast cancer patients receiving chemotherapy plus G-CSF. MiniMACS AC133+ isolated cells contained a mean of 85% (80-90) AC133+ cells. Enriched AC133+ cells coexpressed 80% CD34+, 6.6% CD33+ and 2% CD15+. Separated AC133+ cells contained 600 GFU-GM/10(4) cells and 70 BFU-E/10(4) cells. Flow-cytometric analysis indicated that AC133+ cells were isolated from cells population with low granularity (SS), while CD33+ a CD15+ cells had a high granularity. After a seven-day ex vivo expansion in the presence of SCF + IL-3 + IL11, the expansion of cells increased 19.4 times. The mean percentage of blasts decreased from 100% at the start of culture to 81% on day 3 and 30% on day 7. Promyelocytes were slow to appear with 10% present on day 3, but thereafter increased to 33% on day 7. The appearance of myelocytes and metamyelocytes lagged 3 days behind promyelocytes and continued to increase during culture to become the predominant (30%) cell type on day 7. Very few neutrophils (2%) were observed in any of the cultures on day 7. Monocytes or macrophages were not detected on day 7. By day 7 megakaryocytes were present at low levels (10%). The mean value of CFU-GM in the culture after day 7 of ex vivo expansion in the presence of SCF+IL-3+IL-11 had increased 45-fold, BFU-E 5-fold. After 7 days of expansion with IL-3+SCF+IL-11 cells expressed a mean of 12% CD34+, 8% AC133+, 59% CD33+ and 30% CD15+. The aim of this experiment was to determine whether ex vivo culture of peripheral blood AC133+ cells could generate sufficient numbers of progenitors to potentially abrogate cytopenia after transplantation and passive purging of tumor cells.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • AC133 Antigen
  • Adult
  • Antigens, CD
  • Antigens, CD34 / biosynthesis
  • Antigens, CD34 / blood*
  • Antigens, CD34 / immunology
  • Antineoplastic Combined Chemotherapy Protocols / therapeutic use
  • Breast Neoplasms / blood*
  • Breast Neoplasms / drug therapy
  • Breast Neoplasms / immunology
  • Cyclophosphamide / adverse effects
  • Etoposide / administration & dosage
  • Female
  • Glycoproteins / biosynthesis
  • Glycoproteins / blood*
  • Glycoproteins / immunology
  • Granulocyte Colony-Stimulating Factor / administration & dosage
  • Hematopoietic Cell Growth Factors / pharmacology*
  • Hematopoietic Stem Cell Mobilization
  • Hematopoietic Stem Cells / cytology*
  • Hematopoietic Stem Cells / drug effects*
  • Hematopoietic Stem Cells / immunology
  • Humans
  • Interleukin-11 / pharmacology
  • Interleukin-3 / pharmacology
  • Leukapheresis
  • Middle Aged
  • Peptides / blood*
  • Peptides / immunology
  • Recombinant Proteins / pharmacology
  • Stem Cell Factor / pharmacology

Substances

  • AC133 Antigen
  • Antigens, CD
  • Antigens, CD34
  • Glycoproteins
  • Hematopoietic Cell Growth Factors
  • Interleukin-11
  • Interleukin-3
  • PROM1 protein, human
  • Peptides
  • Recombinant Proteins
  • Stem Cell Factor
  • Granulocyte Colony-Stimulating Factor
  • Etoposide
  • Cyclophosphamide