DNA Damage and Repair in Epithelium after Allogeneic Hematopoietic Stem Cell Transplantation

Abstract

Allogeneic hematopoietic stem cell transplantation (allo-HSCT) in humans, following hematoablative treatment, results in biological chimeras. In this case, the transplanted hematopoietic, immune cells and their derivatives can be considered the donor genotype, while the other tissues are the recipient genotype. The first sequel, which has been recognized in the development of chimerical organisms after allo-HSCT, is the graft versus host (GvH) reaction, in which the new developed immune cells from the graft recognize the host’s epithelial cells as foreign and mount an inflammatory response to kill them. There is now accumulating evidence that this chronic inflammatory tissue stress may contribute to clinical consequences in the transplant recipient. It has been recently reported that host epithelial tissue acquire genomic alterations and display a mutator phenotype that may be linked to the occurrence of a GvH reaction. The current review discusses existing data on this recently discovered phenomenon and focuses on the possible pathogenesis, clinical significance and therapeutic implications.

Primary distal femur T-cell lymphoma after allogeneic haematopoietic stem cell transplantation for chronic myeloid leukaemia: A rare case report and literature review

“…With the increase in the number of haematopoietic stem cell transplantations, more attention is being paid to the occurrence of post-transplantation tumour development. 7–9 A report published in 1999 that analysed data from more than 1000 patients who had undergone bone marrow transplantation showed that the incidence of secondary malignancies was about 3.5% at 10 years and 12.8% at 15 years, which was 3.8-fold higher than that of an age-matched control population. 10 A more recent update of this research published in 2008 indicated that compared with the age-matched control population, the incidence of secondary malignancies was increasing, with a longer follow-up time.…”

Protective effects of alpha phenyl-tert-butyl nitrone and ascorbic acid in human adipose derived mesenchymal stem cells from differently aged donors

“…% tail DNA directly correlates with DNA break frequency and, as such, our data would indicate that both PBN and AA are capable of reducing the frequency of DNA breaks in H 2 O 2 -treated ADSCs. Genotoxic stress has been previously reported to trigger the differentiation of ADSCs into adipocytes [ 21 , 22 ] and complications in DNA damage and repair have been reported following allogeneic transplantation with stem cells [ 36 ]. Therefore, the basal levels of DNA damage in MSCs may affect their efficiency and therapeutic potential following transplantation.…”