Administration of recombinant human granulocyte–colony‐stimulating factor does not induce long‐lasting detectable epigenetic alterations in healthy donors

Leitner, Gerda; Faschingbauer, M.; Wenda, S.; Weigel, Günter; Fischer, Gottfried

doi:10.1111/trf.12732

Cited by 5 publications

(2 citation statements)

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“…Among the differentially expressed genes were genes involved in cellular growth, cell death and survival, protein synthesis, gene expression and nucleic acid metabolism. In another study of twenty stem cell donors, changes of DNA methyltransferase activity in peripheral blood cells were found after G-CSF administration, though these changes returned to baseline within a week after apheresis (Leitner et al 2014). Thus, several studies of donor cells suggest epigenetic changes induced after G-CSF administration in healthy donors, though none of these studies have investigated the global metabolite profile of healthy donors after G-CSF treatment.…”

Section: Discussionmentioning

confidence: 99%

Granulocyte colony-stimulating factor alters the systemic metabolomic profile in healthy donors

2016

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IntroductionPeripheral blood stem cells mobilized by granulocyte colony-stimulating factor (G-CSF) from healthy donors are commonly used for allogeneic stem cell transplantation. The effect of G-CSF administration on global serum metabolite profiles has not been investigated before.ObjectivesThis study aims to examine the systemic metabolomic profiles prior to and following administration of G-CSF in healthy adults.MethodsBlood samples were collected from 15 healthy stem cell donors prior to and after administration of G-CSF 10 µg/kg/day for 4 days. Using a non-targeted metabolomics approach, metabolite levels in serum were determined using ultrahigh performance liquid chromatography-tandem mass spectrometry and gas chromatography/mass spectrometry.ResultsComparison of the metabolite profiles of donors before and after G-CSF treatment revealed 239 metabolites that were significantly altered. The major changes of the metabolite profiles following G-CSF administration included alteration of several fatty acids, including increased levels of several medium and long-chain fatty acids, as well as polyunsaturated fatty acids; while there were lower levels of other lipid metabolites such as phospholipids, lysolipids, sphingolipids. Furthermore, there were significantly lower levels of several amino acids and/or their metabolites, including several amino acids with known immunoregulatory functions (methionine, tryptophan, valine). Lastly, the levels of several nucleotides and nucleotide metabolites (guanosine, adenosine, inosine) were also decreased after G-CSF administration, while methylated products were increased. Some of these altered products/metabolites may potentially have angioregulatory effects whereas others may suggest altered intracellular epigenetic regulation.ConclusionOur results show that G-CSF treatment alters biochemical serum profiles, in particular amino acid, lipid and nucleotide metabolism. Additional studies are needed to further evaluate the relevance of these changes in healthy donors.Electronic supplementary materialThe online version of this article (doi:10.1007/s11306-016-1139-x) contains supplementary material, which is available to authorized users.

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Section: Discussionmentioning

confidence: 99%

Granulocyte colony-stimulating factor alters the systemic metabolomic profile in healthy donors

2016

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“…The influence of G-CSF on DNA methyltransferase (DNMT) activity and on changes in DNA methylation of candidate genes has been analyzed in peripheral blood cells of 20 healthy unrelated stem cell donors within an observation period of 1 year [ 78 ]. The authors performed methylation-specific PCR to detect the methylation status of promoter CpG islands of retinoic acid receptor β ( RAR - B ) gene and Ras association domain family 1A ( RASSF1A ) gene.…”

Section: Ethical and Safety Issues Related To G-csf Administration Tomentioning

confidence: 99%

Granulocyte transfusions in children and adults with hematological malignancies: benefits and controversies

et al. 2015

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Bacterial and fungal infections continue to pose a major clinical challenge in patients with prolonged severe neutropenia after chemotherapy or hematopoietic stem cell transplantation (HSCT). With the advent of granulocyte colony-stimulating factor (G-CSF) to mobilize neutrophils in healthy donors, granulocyte transfusions have been broadly used to prevent and/or treat life-threatening infections in patients with severe febrile neutropenia and/or neutrophil dysfunction. Although the results of randomized controlled trials are inconclusive, there are suggestions from pilot and retrospective studies that granulocyte transfusions may benefit selected categories of patients. We will critically appraise the evidence related to the use of therapeutic granulocyte transfusions in children and adults, highlighting current controversies in the field and discussing complementary approaches to modulate phagocyte function in the host.

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The Safety of Allogeneic Stem Cell Transplantation

Hütter

2017

Stem Cells in Clinical Applications

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Administration of recombinant human granulocyte–colony‐stimulating factor does not induce long‐lasting detectable epigenetic alterations in healthy donors

Abstract: In our prospective study no evidence of long-lasting increased DNMT activity or enhanced DNA methylation in a limited panel of target genes after recombinant human G-CSF administration was observed in healthy stem cell donors.

Cited by 5 publications

References 32 publications

Granulocyte colony-stimulating factor alters the systemic metabolomic profile in healthy donors

Granulocyte colony-stimulating factor alters the systemic metabolomic profile in healthy donors

Granulocyte transfusions in children and adults with hematological malignancies: benefits and controversies

The Safety of Allogeneic Stem Cell Transplantation

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