Comparison of gene expression in CD34(+) cells from bone marrow and G-CSF-mobilized peripheral blood by high-density oligonucleotide array analysis

A prospective randomized trial has shown that there is a survival advantage for allogeneic transplant recipients who received granulocyte colony-stimu lating factor (G-CSF)-stimulated peripheral blood mononuclear cells (GPBMC) versus those who received bone marrow (BM) as a source of stem cells. The biological basis for this advantage is not clear and may be attributable to qualitative as well as quantitative differences in the CD34 cells, T cells , and/or the monocytes transplanted. To begin to address this issue, gene e xpression patterns in CD34 cells isolated from these 2 stem cell sources we re compared to identify functional pathways that may distinguish these 2 po pulations. CD34 cells were isolated to purity from the BM and peripheral bl ood stem cells of multiple healthy donors. (The complete data set mill be a vailable at http://parma.fhcrc.org/Igraf upon publication.) Two separate RN A preparations from pooled samples from both sources were analyzed by Affym etrix Oligonucleotide Array chips for expression of over 6400 human genes. Comparative analyses among the samples showed that a small set of 28 sequen ces increased and 38 sequences decreased in expression more than 3-fold in both of the GPBMC samples compared to those in BM samples. More highly expr essed genes include several for nuclear proteins and transcriptional factor s. Functional categorization of the genes decreased in expression indicated sequences influential in cell cycle progression, in agreement with the rec ognized quiescence of circulating CD34 cells. Multiple transcriptional regu lators and chemokines were also found to be decreased. These data emphasize that in addition to increased numbers of CD34 cells, G-CSF mobilization al so results in significant qualitative changes. Whether they impact engraftm ent remains to be determined.