Quantitative analysis of Fas and bcl-2 expression in hematopoietic precursors

Haematologica. 2001 Mar;86(3):237-43.

Abstract

Background and objectives: We investigated the expression of bcl-2 and CD95 (Apo1-/Fas) on CD34+ cells obtained from bone marrow (BM), mobilized peripheral blood (MPB), and umbilical cord blood (UCB) samples. The expression of bcl-2 and Fas was then compared with that of other markers usually associated with immaturity; functional tests using the agonistic antibody anti- Fas CH11 were also carried out.

Design and methods: The analysis was performed by flow cytometry on purified CD34+ cells in a three (CD95 PE, CD34 APC and CD71 FITC) and in a four (CD38 PE, HLA-DR PerCP, CD34 APC and bcl-2 FITC) fluorescence assay.

Results: The results were expressed as mean fluorescence index (MFI); bcl-2 expression was significantly higher (p < 0.001) in BM (3.73 +/- 0.63) than in MPB (2.47 +/- 0.39) and UCB (2.38 +/- 0.58); Fas was significantly less expressed (p < 0.001) in UCB (1.27 +/- 0.78) than in MBP (3.63 +/- 2.19) and BM (4.56 +/- 1.69). CD34 expression was significantly (p < 0.001) brighter in UCB compared to in MBP and BM, while CD38 and CD71 were significantly (p = 0.005 and p < 0.001, respectively) more expressed in BM than in MPB and UCB. Fas values were directly correlated to CD38; both Fas and bcl-2 were directly related to CD71 and inversely to CD34. Culture assays showed that hematopoietic precursor cells from BM, MPB and UCB had a low susceptibility to undergo Fas-mediated apoptosis.

Interpretation and conclusions: In conclusion, bcl-2 and Fas are less expressed in UCB than in MPB and BM; early hematopoietic precursor cells are relatively resistant to CD95-triggered apoptosis; the observed correlation between Fas/bcl-2 and markers of immaturity suggests that they may be determinants of commitment in early hematopoietic precursors.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Antigens, CD34 / analysis
  • Blood Cells / immunology
  • Blood Cells / metabolism
  • Bone Marrow Cells / immunology
  • Bone Marrow Cells / metabolism
  • Fetal Blood / cytology
  • Fetal Blood / immunology
  • Fetal Blood / metabolism
  • Hematopoietic Stem Cells / immunology
  • Hematopoietic Stem Cells / metabolism*
  • Humans
  • Leukemia, Lymphoid / pathology
  • Proto-Oncogene Proteins c-bcl-2 / biosynthesis*
  • Proto-Oncogene Proteins c-bcl-2 / metabolism
  • fas Receptor / biosynthesis*
  • fas Receptor / metabolism

Substances

  • Antigens, CD34
  • Proto-Oncogene Proteins c-bcl-2
  • fas Receptor