Deciphering bone marrow engraftment after allogeneic stem cell transplantation in humans using single cell analyses.
J Clin Invest
; 2024 Aug 29.
Article
em En
| MEDLINE
| ID: mdl-39207851
ABSTRACT
BACKGROUND:
Donor cell engraftment is a pre-requisite of successful allogeneic hematopoietic stem cell transplantation. Based on peripheral blood analyses it is characterized by early myeloid recovery and T- and B-cells lymphopenia. However, cellular networks associated with bone marrow engraftment of allogeneic human cells have been poorly described.METHODS:
Mass cytometry and CITEseq analyses were performed on bone marrow cells, three months post-transplant in patients with acute myelogenous leukemia.RESULTS:
Mass cytometry in 26 patients and 20 healthy controls disclosed profound alterations in myeloid and B-cell progenitors, with a shift towards terminal myeloid differentiation and decreased B-cell progenitors. Unsupervised analysis separated recipients into 2 groups, one of them being driven by previous GVHD (R2 patients). We then used single-cell CITEseq to decipher engraftment, which resolved 36 clusters, encompassing all bone marrow cellular components. Hematopoiesis in transplant recipients was sustained by committed myeloid and erythroid progenitors in a setting of monocytes-, NK cells- and T-cells mediated inflammation. Gene expression disclosed major pathways in transplant recipients, namely, TNFα signaling via NFκ-B, and interferon-γ response. The hallmark of allograft rejection was consistently found in clusters from transplant recipients, especially in R2 recipients.CONCLUSION:
Bone marrow cell engraftment of allogeneic donor cells is characterized by a state of emergency hematopoiesis in the setting of allogeneic response driving inflammation. TRIAL REGISTRATION Not applicable.FUNDING:
This study has been supported by the French National Cancer Institute (Institut National du Cancer) PLBIO19-239 and by an unrestricted research grant by Alexion Pharmaceutical.
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MEDLINE
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En
Ano de publicação:
2024
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Article