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

PLoS One. 2016 Dec 20;11(12):e0168210. doi: 10.1371/journal.pone.0168210. eCollection 2016.

Abstract

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-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.

Publication types

  • Clinical Trial
  • Comparative Study

MeSH terms

  • Adolescent
  • Adult
  • Allografts
  • Dinucleotide Repeats*
  • Disease-Free Survival
  • Female
  • Hematologic Diseases* / genetics
  • Hematologic Diseases* / mortality
  • Hematologic Diseases* / therapy
  • Hematopoietic Stem Cell Transplantation*
  • Heme Oxygenase-1 / genetics*
  • Humans
  • Male
  • Middle Aged
  • Polymorphism, Genetic*
  • Promoter Regions, Genetic*
  • Survival Rate
  • Transplantation Conditioning*
  • Unrelated Donors*

Substances

  • HMOX1 protein, human
  • Heme Oxygenase-1

Grants and funding

This work was funded by the Danish Cancer Society (TK), www.cancer.dk, The Danish Medical Research Counsil (PTS), http://ufm.dk/en/research-and-innovation/councils-and-commissions/the-danish-council-for-independent-research, and Toyota Fonden (PTS). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.