GTn repeat polymorphism in heme oxygenase-1 (HO-1) correlates with clinical outcome after myeloablative or nonmyeloablative allogeneic hematopoietic cell transplantation
Research output: Contribution to journal › Journal article › peer-review
Standard
GTn repeat polymorphism in heme oxygenase-1 (HO-1) correlates with clinical outcome after myeloablative or nonmyeloablative allogeneic hematopoietic cell transplantation. / 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, Eivind Per.
In: PLoS ONE, Vol. 11, No. 12, e0168210, 12.2016.Research output: Contribution to journal › Journal article › peer-review
Harvard
APA
Vancouver
Author
Bibtex
}
RIS
TY - JOUR
T1 - GTn repeat polymorphism in heme oxygenase-1 (HO-1) correlates with clinical outcome after myeloablative or nonmyeloablative allogeneic hematopoietic cell transplantation
AU - Køllgaard, Tania
AU - Kornblit, Brian
AU - Petersen, Jesper
AU - Klausen, Tobias Wirenfeldt
AU - Mortensen, Bo Kok
AU - Brændstrup, Peter
AU - Sengeløv, Henrik
AU - Høgdall, Estrid
AU - Müller, Klaus
AU - Vindeløv, Lars
AU - Andersen, Mads Hald
AU - thor Straten, Eivind Per
PY - 2016/12
Y1 - 2016/12
N2 - 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 ratelimiting 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- 1high 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-1low donor cells into HO-1low 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.
AB - 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 ratelimiting 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- 1high 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-1low donor cells into HO-1low 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.
U2 - 10.1371/journal.pone.0168210
DO - 10.1371/journal.pone.0168210
M3 - Journal article
C2 - 27997582
AN - SCOPUS:85006961102
VL - 11
JO - PLoS ONE
JF - PLoS ONE
SN - 1932-6203
IS - 12
M1 - e0168210
ER -
ID: 180939548