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Graft-Versus-Host Disease

Increased apoptosis is linked to severe acute GVHD in patients with Fanconi anemia

Bone Marrow Transplantation volume 48, pages 849–853 (2013)Cite this article

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Abstract

Fanconi anemia (FA) patients have an increased risk of acute GVHD (aGVHD) after hematopoietic SCT, with hypersensitivity to DNA-cross-linking agents and defective DNA repair. MicroRNA-34 and p53 can induce apoptosis after DNA damage.Here we assessed epithelial cell apoptosis, and studied TP53 and miR-34a expression in the skin and gut biopsies in five non-transplanted FA patients, in 20 FA patients with aGVHD and in 25 acquired aplastic anemia patients (AA). Epithelial apoptosis was higher in FA than in acquired AA patients in both the skin and gut biopsies, though they had a similar preparative regimen. Further study on gut biopsies in FA patients showed that this deleterious effect was not linked to TP53 gene overexpression. As, among p53-independent signaling pathways of apoptosis, the microRNA-34 family mimics p53 apoptotic effects in response to DNA damage, we studied miR-34a expression in the same series of FA patients’ gut biopsies. MiR-34a expression level was higher in severe aGVHD compared with non-aGVHD subjects or non-transplanted patients, and significantly related to apoptotic cell numbers across the three groups of FA patients. Thus, in FA patients, increased apoptosis occurs in target epithelial cells of severe aGVHD, and this deleterious effect is linked to overexpression of miR-34a but not TP53.

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Acknowledgements

We thank Mrs Angela Swaine Verdier who reviewed the English language of the manuscript. This work was supported by the University Paris Diderot, Inserm, ANR, InCa. Li Wang was supported by Inserm with an International ‘Poste vert’.

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Author notes

  1. L Wang & M Romero

    Present address: Departamento de Patología, Hospital Universitario Fundación Santa Fe de Bogotá-Universidad de los Andes, Calle 119 No. 7-75. Bogotá, Colombia.,

  2. M Romero: These authors contributed equally to this work.

  3. R Peffault de Latour and W-L Zhao: These authors contributed equally to this work.

Authors and Affiliations

  1. Inserm, U728, Paris, France

    L Wang, M Romero, P Ratajczak, C Lebœuf, S Belhadj, R Peffault de Latour, W-L Zhao, G Socié & A Janin

  2. Université Paris Diderot, Sorbonne Paris Cité, Laboratoire de Pathologie, Hôpital Saint-Louis, Paris, France

    L Wang, M Romero, P Ratajczak, C Lebœuf, S Belhadj, R Peffault de Latour, W-L Zhao, G Socié & A Janin

  3. Department of Pathology, AP-HP, Hôpital Saint-Louis, Paris, France

    P Ratajczak, S Belhadj & A Janin

  4. Department of Bone Marrow Transplant, AP-HP, Hôpital Saint-Louis, Paris, France

    R Peffault de Latour & G Socié

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Correspondence to A Janin.

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Wang, L., Romero, M., Ratajczak, P. et al. Increased apoptosis is linked to severe acute GVHD in patients with Fanconi anemia. Bone Marrow Transplant 48, 849–853 (2013). https://doi.org/10.1038/bmt.2012.237

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