Cargando…

(GT)(n) Repeat Polymorphism in Heme Oxygenase-1 (HO-1) Correlates with Clinical Outcome after Myeloablative or Nonmyeloablative Allogeneic Hematopoietic Cell Transplantation

Allogeneic hematopoietic cell transplantation (HCT) is a treatment for various hematologic diseases where efficacy of treatment is in part based on the graft versus tumour (GVT) activity of cells in the transplant. The cytoprotective enzyme heme oxygenase-1 (HO-1) is a rate-limiting enzyme in heme d...

Descripción completa

Detalles Bibliográficos
Autores principales: Køllgaard, Tania, Kornblit, Brian, Petersen, Jesper, Klausen, Tobias Wirenfeldt, Mortensen, Bo Kok, Brændstrup, Peter, Sengeløv, Henrik, Høgdall, Estrid, Müller, Klaus, Vindeløv, Lars, Andersen, Mads Hald, thor Straten, Per
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Public Library of Science 2016
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5172582/
https://www.ncbi.nlm.nih.gov/pubmed/27997582
http://dx.doi.org/10.1371/journal.pone.0168210
Descripción
Sumario:Allogeneic hematopoietic cell transplantation (HCT) is a treatment for various hematologic diseases where efficacy of treatment is in part based on the graft versus tumour (GVT) activity of cells in the transplant. The cytoprotective enzyme heme oxygenase-1 (HO-1) is a rate-limiting enzyme in heme degradation and it has been shown to exert anti-inflammatory functions. In humans a (GT)(n) repeat polymorphism regulates the expression of HO-1. We conducted fragment length analyses of the (GT)(n) repeat in the promotor region of the gene for HO-1 in DNA from donors and recipients receiving allogeneic myeloablative- (MA) (n = 110) or nonmyeloablative- (NMA-) (n = 250) HCT. Subsequently, we compared the length of the (GT)(n) repeat with clinical outcome after HCT. We demonstrated that transplants from a HO-1(high) donor after MA-conditioning (n = 13) is associated with higher relapse incidence at 3 years (p = 0.01, n = 110). In the NMA-conditioning setting transplantation of HO-1(low) donor cells into HO-1(low) recipients correlated significantly with decreased relapse related mortality (RRM) and longer progression free survival (PFS) (p = 0.03 and p = 0.008, respectively). Overall, our findings suggest that HO-1 may play a role for the induction of GVT effect after allogeneic HCT.