Alterations of circulating lymphoid committed progenitor cellular metabolism after allogeneic stem cell transplantation in humans.
Lymphoid-committed CD34(+)lin(-)CD10(+)CD24(-) progenitors undergo a rebound at month 3 after allogeneic hematopoietic stem cell transplantation (allo-HSCT) in the absence of acute graft-versus-host disease (aGVHD). Here, we analyzed transcriptional programs of cell-sorted circulating lymphoid-committed progenitors and CD34(+)Lin(-)CD10(-) nonlymphoid progenitors in 11 allo-HSCT patients who had (n = 5) or had not (n = 6) developed grade 2 or 3 aGVHD and in 7 age-matched healthy donors. Major upregulated pathways include protein synthesis, energy production, cell cycle regulation, and cytoskeleton organization. Notably, genes from protein biogenesis, translation machinery, and cell cycle (CDK6) were overexpressed in progenitors from patients in the absence of aGVHD compared with healthy donors and patients affected by aGVHD. Expression of many genes from the mitochondrial oxidative phosphorylation metabolic pathway leading to ATP production were more specifically increased in lymphoid-committed progenitors in the absence of aGVHD. This was also the case for genes involved in cell mobilization such as those regulating Rho GTPase activity. In all, we found that circulating lymphoid-committed progenitors undergo profound changes in metabolism, favoring cell proliferation, energy production, and cell mobilization after allo-HSCT in humans. These mechanisms are abolished in the case of aGVHD or its treatment, indicating a persistent cell-intrinsic defect after exit from the bone marrow.
Institut Universitaire d'Hématologie, Université Paris Diderot, Sorbonne Paris Cité, Paris, France; INSERM UMR 1160, Paris, France; Laboratoire d'Immunologie et d'Histocompatibilité, Hôpital Saint-Louis, AP-HP, Paris, France.
Salomé
S
Glauzy
Service d'Hématologie-Greffe de Moelle, Hôpital Saint-Louis, AP-HP, Paris, France.
Régis
R
Peffault de Latour
Institut Imagine, Paris, France; Hôpital Necker, Université Paris Descartes, Sorbonne Paris Cité, Paris, France.
Isabelle
I
André-Schmutz
ProfilXpert, Lyon, France.
Joël
J
Lachuer
Service d'Hématologie-Greffe de Moelle, Hôpital Saint-Louis, AP-HP, Paris, France.
Sophie
S
Servais
Institut Universitaire d'Hématologie, Université Paris Diderot, Sorbonne Paris Cité, Paris, France; INSERM UMR 1160, Paris, France; Service d'Hématologie-Greffe de Moelle, Hôpital Saint-Louis, AP-HP, Paris, France.
Gérard
G
Socié
Institut Universitaire d'Hématologie, Université Paris Diderot, Sorbonne Paris Cité, Paris, France; INSERM UMR 1160, Paris, France; Laboratoire d'Immunologie et d'Histocompatibilité, Hôpital Saint-Louis, AP-HP, Paris, France. Electronic address: emmanuel.clave@univ-paris-diderot.fr.
Emmanuel
E
Clave
Institut Universitaire d'Hématologie, Université Paris Diderot, Sorbonne Paris Cité, Paris, France; INSERM UMR 1160, Paris, France; Laboratoire d'Immunologie et d'Histocompatibilité, Hôpital Saint-Louis, AP-HP, Paris, France.
Antoine
A
Toubert
D000328:Adult; D015415:Biomarkers; D004734:Energy Metabolism; D005260:Female; D006086:Graft vs Host Disease / Q000175:diagnosis / Q000209:etiology; D018380:Hematopoietic Stem Cell Transplantation / Q000009:adverse effects; D006801:Humans; D016130:Immunophenotyping; D054503:Lymphoid Progenitor Cells / Q000378:metabolism*; D008297:Male; D008875:Middle Aged; D010641:Phenotype; D014184:Transplantation, Homologous; D055815:Young Adult
D015415:Biomarkers